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2.
Inflamm Res ; 58(4): 204-9, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19169648

RESUMO

OBJECTIVE: Mice selected for a strong (AIRmax) or weak (AIRmin) acute inflammatory response present different susceptibilities to bacterial infections, autoimmune diseases and carcinogenesis. Variations in these phenotypes have been also detected in AIRmax and AIRmin mice rendered homozygous for Slc11a1 resistant (R) and susceptible (S) alleles. Our aim was to investigate if the phenotypic differences observed in these mice was related to the complement system. MATERIAL: AIRmax and AIRmin mice and AIRmax and AIRmin groups homozygous for the resistance (R) or susceptibility (S) alleles of the solute carrier family 11a1 member (Slc11a1) gene, formerly designated Nramp-1. METHODS AND RESULTS: While no difference in complement activity was detected in sera from AIRmax and AIRmin strains, all sera from AIRmax Slc11a1 resistant mice (AIRmax(RR)) presented no complement-dependent hemolytic activity. Furthermore, C5 was not found in their sera by immunodiffusion and, polymerase chain reaction and DNA sequencing of its gene demonstrated that AIRmax(RR) mice are homozygous for the C5 deficient (D) mutation previously described in A/J. Therefore, the C5D allele was fixed in homozygosis in AIRmax(RR) line. CONCLUSIONS: The AIRmax(RR) line is a new experimental mouse model in which a strong inflammatory response can be triggered in vivo in the absence of C5.


Assuntos
Complemento C5 , Inflamação/genética , Camundongos Endogâmicos , Animais , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/imunologia , Ativação do Complemento , Complemento C5/genética , Complemento C5/imunologia , Via Alternativa do Complemento/imunologia , Feminino , Predisposição Genética para Doença , Hemólise , Inflamação/imunologia , Masculino , Camundongos , Camundongos Endogâmicos/genética , Camundongos Endogâmicos/imunologia
3.
Genes Immun ; 8(1): 51-6, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17122779

RESUMO

Mice selected for the maximum acute inflammatory reaction (AIRmax) are highly susceptible to pristane-induced arthritis (PIA), whereas mice selected for the minimum response (AIRmin) are resistant. These lines show distinct patterns of leukocyte infiltration and R and S allele frequency disequilibrium of the solute carrier family 11a member 1 (Slc11a1) gene. In order to study the interactions of the Slc11a1 R and S alleles with the inflammation modulating Quantitative Trait Loci (QTL) during PIA development, homozygous AIRmax(RR), AIRmax(SS), AIRmin(RR) and AIRmin(SS) lines were produced by genotype-assisted breedings. These mice received two intraperitoneal injections of 0.5 ml pristane at 60-day intervals, and the subsequent development of arthritis was assessed for 210 days. Cytokine-secreting cell profiles were investigated using enzyme-linked immunospot. Arthritis incidence in AIRmax(RR) mice reached 29%, whereas PIA incidence in AIRmax(SS) mice was 70% by day 180. AIRmin(RR) mice were resistant, whereas 13.3% of AIRmin(SS) mice became arthritic. The presence of the defective S allele also increased arthritis severity, although acute inflammation was higher in mice bearing the R allele. A predominant Th0/Th2-type response in Slc11a1(SS) mice was observed. These results indicate that Slc11a1 is a strong candidate for the QTL modulating acute inflammation and for PIA.


Assuntos
Artrite Reumatoide/genética , Proteínas de Transporte de Cátions/genética , Predisposição Genética para Doença , Inflamação/genética , Terpenos , Alelos , Animais , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/imunologia , Cromossomos de Mamíferos , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Frequência do Gene , Inflamação/imunologia , Masculino , Camundongos , Camundongos Endogâmicos , Repetições de Microssatélites , Locos de Características Quantitativas , Baço/citologia
4.
J. venom. anim. toxins incl. trop. dis ; J. venom. anim. toxins incl. trop. dis;13(1): 39-55, 2007. graf, ilus
Artigo em Inglês | LILACS, Sec. Est. Saúde SP | ID: lil-444610

RESUMO

Rabies is a severe and lethal disease that produces a slight inflammatory response during the infection process. We analyzed the immunopathological mechanisms that occur in the central nervous system (CNS) using mice genetically selected for maximal or minimal acute inflammatory reaction (AIRmax or AIRmin). As viral samples, we adopted the antigenic variant 3 (AgV3) of rabies virus from hematophagous bats and a fixed virus strain (PV1 43/3). Titration of specific antibodies was performed using enzyme-linked immunosorbent assay (ELISA). We observed a slight increase in IgG and IgG1 isotypes in infected AIRmax mice. Incubation period, determined by intracerebral inoculation with 100 LD50, was 6-7 days for PV1 43/4 strain and 9-10 days for AgV3. No difference in viral replication was noticed between AIRmax and AIRmin mice. Mortality was 100 percent with both viral strains. Histopathological analysis of brains and spinal cords showed inflammatory foci in all regions of the CNS. No differences were noticed in the number of neutrophils. Negri bodies were observed in practically all sites analyzed. Results suggested that inflammatory reaction is not a determining factor in the susceptibility to rabies infection.


Assuntos
Ratos , Animais , Masculino , Feminino , Inflamação , Raiva/fisiopatologia , Raiva/imunologia , Raiva/patologia , Reação de Fase Aguda , Camundongos , Replicação Viral , Sistema Nervoso Central
5.
Clin Exp Allergy ; 36(11): 1399-407, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17083350

RESUMO

BACKGROUND: Immunological oral tolerance is being studied with great interest due to its therapeutic potential in allergy and autoimmunity processes, although the cellular and molecular mechanisms linking these different phenomena remain elusive. In the present study, two mouse lines with extreme phenotypes for susceptibility [TS Line] or resistance [TR Line] to oral tolerance and their [TS x TR]F2 segregants were used in order to evaluate the impact of these traits on the atopic potential of the individuals. OBJECTIVE: Demonstrate whether the tr and ts genes, cumulated during 18 generations of bidirectional genetic selection, influence expression of two important immunobiological traits (IgE and mast cell) critical to allergic response. METHODS: Mice with extreme phenotypes for oral tolerance to ovalbumin (OVA), produced by assortative mating (TS and TR Line), and their (TS x TR)F2 segregating were used. Serum IgE levels assayed by ELISA, and mastocytes counted with toluidine blue staining were evaluated in naïve mice. Anaphylaxis was induced by intravenous injection of OVA, intestinal inflammation by oral administration of OVA 7 days after immunization, and pulmonary inflammation by intranasal and nebulization OVA challenges. Specific IgE was dosed by passive cutaneous anaphylaxis. RESULTS: The naïve TS mice have a 20-fold lower serum IgE level and two- to threefold diminished mast cell numbers in mucosal sites, when compared with TR-mice, which were highly susceptible to allergic inflammation and anaphylactic shock. The associations of oral tolerance, serum IgE levels and mast cell numbers in naïve animals were confirmed analysing the simultaneous presence of these traits in individuals of a [TS x TR]F2 -segregating population. CONCLUSION: The results suggest that the complex of genes controlling TS and TR phenotypes play a main role in the regulation of the atopic potential of the individual. The studies of these traits in interline F2 segregants demonstrated a co-segregation of TS and TR phenotypes with IgE responsiveness and mast cell numbers. Thus, the opposite capacity of the genetically modified mice may be involved in co-adaptative mechanisms reflecting a dynamic relation between gene frequencies in a natural population. These correlations give circumstantial evidence to support clinical applications of oral tolerance in allergic and autoimmune diseases.


Assuntos
Hipersensibilidade/genética , Imunoglobulina E/sangue , Mastócitos/patologia , Mucosa/imunologia , Administração Oral , Animais , Animais não Endogâmicos , Cruzamento , Líquido da Lavagem Broncoalveolar/imunologia , Contagem de Células , Predisposição Genética para Doença , Genótipo , Hipersensibilidade/imunologia , Imunidade Inata , Imunoglobulina E/imunologia , Mucosa Intestinal/imunologia , Camundongos , Ovalbumina , Anafilaxia Cutânea Passiva , Fenótipo , Mucosa Respiratória/imunologia
6.
Genes Immun ; 7(1): 44-50, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16435023

RESUMO

Mice obtained by bidirectional selective breeding for high (HIII) or low (LIII) antibody (Ab) production are resistant or extremely susceptible to pristane-induced arthritis (PIA), respectively. Several quantitative trait loci regulating Ab production (Ab QTL) have been mapped in these lines, which were used to investigate the influence of these Ab QTL in PIA. Parental HIII and LIII mice and their F1 and F2 intercrosses were injected twice with pristane, and arthritis was observed for 200 days. In LIII mice PIA was more severe and incidence was 100% at day 105, while F1 and F2 mice showed intermediate values. HIII mice were totally resistant. Microsatellite polymorphisms of Ab QTL were analysed and D3Mit100 alleles cosegregated significantly with PIA incidence, severity and onset in F2 intercross mice, while the other four markers showed suggestive values. Results indicate colocalization of QTL for Ab production and PIA susceptibility. Moreover, the different cytokine and IgG isotype profiles observed in HIII and LIII lines after PIA induction are useful to candidate genes endowed with the regulation of the Ab production and arthritis phenotypes.


Assuntos
Artrite Experimental/genética , Artrite Experimental/imunologia , Autoanticorpos/biossíntese , Predisposição Genética para Doença , Locos de Características Quantitativas , Animais , Artrite Experimental/induzido quimicamente , Cruzamentos Genéticos , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Camundongos Endogâmicos , Repetições de Microssatélites , Terpenos/toxicidade
7.
Rev. bras. pesqui. méd. biol ; Braz. j. med. biol. res;38(12): 1807-1815, Dec. 2005. ilus
Artigo em Inglês | LILACS | ID: lil-417189

RESUMO

Mice selected on the basis of an acute inflammatory response (AIR) can provide information about the immunopathological mechanisms of glomerulonephritis. We studied the differences between mice selected for a maximal AIR (AIRmax that attract more polymorphonuclear cells to the site of injury) or a minimal AIR (AIRmin that attract more mononuclear cells) in an experimental model of IgA nephropathy in order to investigate the effect of genetic background on glomerular disease progression and the participation of the monocyte chemoattractant protein-1 (MCP-1) chemokine. IgA nephropathy was induced by intraperitoneal ovalbumin injection and bile duct ligation in AIRmax and AIRmin mice. Histological changes, urinary protein/creatinine ratio, serum IgA levels, immunofluorescence for IgA, IgG and complement C3 fraction, immunohistochemistry for macrophages and MCP-1, and MCP-1 levels in macerated kidney were determined. Mesangial IgA deposition was seen only in AIRmin mice, which presented more renal lesions. Increased serum IgA levels (1.5 ± 0.4 vs 0.3 ± 0.1 mg/mL, P < 0.001), high glomerular MCP-1 expression and decreased monocyte/macrophage infiltration in the interstitial area (0.3 ± 0.3 vs 1.1 ± 0.9 macrophages/field, P < 0.05) were detected in AIRmin mice compared to AIRmax mice. No glomerular monocyte/macrophage infiltration was detected in either strain. In spite of the absence of IgA deposition, AIRmax mice presented discrete or absent mesangial proliferation. The study showed that there are differences between mice selected for AIRmax and AIRmin with respect to serum IgA levels, histological damage and MCP-1 chemokine production after ovalbumin injection in combination with bile duct ligation.


Assuntos
Animais , Masculino , Feminino , Camundongos , Glomerulonefrite por IGA/genética , Glomerulonefrite por IGA/imunologia , Inflamação/imunologia , Macrófagos/imunologia , Monócitos/imunologia , /imunologia , Doença Aguda , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Especificidade da Espécie , Glomerulonefrite por IGA/patologia , Imuno-Histoquímica , Inflamação/patologia , Camundongos Endogâmicos BALB C , Macrófagos/patologia , Monócitos/fisiologia , Reação de Fase Aguda/imunologia , Reação de Fase Aguda/patologia
8.
Braz J Med Biol Res ; 38(12): 1807-15, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16302095

RESUMO

Mice selected on the basis of an acute inflammatory response (AIR) can provide information about the immunopathological mechanisms of glomerulonephritis. We studied the differences between mice selected for a maximal AIR (AIRmax that attract more polymorphonuclear cells to the site of injury) or a minimal AIR (AIRmin that attract more mononuclear cells) in an experimental model of IgA nephropathy in order to investigate the effect of genetic background on glomerular disease progression and the participation of the monocyte chemoattractant protein-1 (MCP-1) chemokine. IgA nephropathy was induced by intraperitoneal ovalbumin injection and bile duct ligation in AIRmax and AIRmin mice. Histological changes, urinary protein/creatinine ratio, serum IgA levels, immunofluorescence for IgA, IgG and complement C3 fraction, immunohistochemistry for macrophages and MCP-1, and MCP-1 levels in macerated kidney were determined. Mesangial IgA deposition was seen only in AIRmin mice, which presented more renal lesions. Increased serum IgA levels (1.5 +/- 0.4 vs 0.3 +/- 0.1 mg/mL, P < 0.001), high glomerular MCP-1 expression and decreased monocyte/macrophage infiltration in the interstitial area (0.3 +/- 0.3 vs 1.1 +/- 0.9 macrophages/field, P < 0.05) were detected in AIRmin mice compared to AIRmax mice. No glomerular monocyte/macrophage infiltration was detected in either strain. In spite of the absence of IgA deposition, AIRmax mice presented discrete or absent mesangial proliferation. The study showed that there are differences between mice selected for AIRmax and AIRmin with respect to serum IgA levels, histological damage and MCP-1 chemokine production after ovalbumin injection in combination with bile duct ligation.


Assuntos
Quimiocina CCL2/imunologia , Glomerulonefrite por IGA/genética , Glomerulonefrite por IGA/imunologia , Inflamação/imunologia , Macrófagos/imunologia , Monócitos/imunologia , Doença Aguda , Reação de Fase Aguda/imunologia , Reação de Fase Aguda/patologia , Animais , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Glomerulonefrite por IGA/patologia , Imuno-Histoquímica , Inflamação/patologia , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Monócitos/fisiologia , Especificidade da Espécie
9.
Toxicon ; 43(7): 761-8, 2004 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-15284010

RESUMO

Lines of mice genetically selected for high (H) or low (L) antibody response and for maximal (AIRMAX) or minimal (AIRMIN) acute inflammatory reaction, in which the opposite extreme potentialities have been clearly defined, offer an appropriate model for investigating the environmental and genetic factors acting on innate and adaptative immunobiological functions. This model has been successfully employed to study the resistance or susceptibility against pathogens and/or toxins. It had been demonstrated that the skin contact with Lonomia obliqua caterpillar bristles induces local inflammation and may elicit severe hemorrhagic disorders. In the present study, blood coagulation time, and the acute inflammatory reaction were scored 24 h after injection of the Lonomia bristles crude extract in a subcutaneous dorsal air pouch. The acute inflammation was determined by the leukocyte concentration in the local exudates. The highest interline differences were observed between the AIRMAX (10(6) cells/ml) and AIRMIN (2 x 10(5) cells/ml) and this distinct expression involves the number of monocytes, eosinophils and mainly neutrophils. Regarding coagulation, the highest interline difference was observed between the HIII and LIII mice, and the F1)[LIII x HIII] hybrids showed the overdominance of the fast clotting character. The adaptative immune response was evaluated by comparing the anti-Lonomia bristle extract IgG titer among the lines: the antibody titers were higher in the H lines than in the L ones and equivalent in the AIRMAX and AIRMIN mice, in accordance to the phenotype profiles generated by the distinct selective processes. The genetically selected mice lines-AIRMAX, AIRMIN, HI, HIII, HG, LIII and LG-showed an almost continuous distributions for inflammation, coagulation time and IgG antibody titers, being the interline variances always higher than the intraline ones for the individually measured phenotypes. Altogether, these results suggest the independent polygenic regulation of these traits, being indicative of the genetic control to Lonomia toxin innate and adaptative sensitivity in humans.


Assuntos
Venenos de Artrópodes/toxicidade , Imunização , Mariposas/química , Análise de Variância , Animais , Venenos de Artrópodes/imunologia , Coagulação Sanguínea/efeitos dos fármacos , Cruzamentos Genéticos , Ensaio de Imunoadsorção Enzimática , Granulócitos/efeitos dos fármacos , Imunoglobulina G/metabolismo , Inflamação/induzido quimicamente , Contagem de Leucócitos , Camundongos , Especificidade da Espécie
10.
Microbes Infect ; 3(3): 215-22, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11358715

RESUMO

Two strains of mice genetically selected for extreme phenotypes of immunological tolerance to ovalbumin, susceptible (TS) and resistant (TR), were experimentally infected with Sporothrix schenckii. The objective was to observe whether the genetic modifications produced by the selection might be associated with interstrain differences in adaptive immune and innate responses to infection. Therefore, we evaluated the LD(50), CFU, phagocytic index, fungicidal activity, pro-inflammatory cytokines, specific antibody titres, and the delayed-type hypersensitivity reactivity. TR mice were tenfold more susceptible to infection than TS mice, as shown by LD(50) (5 x 10(6) conidia i.v.). In TS mice, the resistance was a consequence of the tissue fungal load reduction, consistent specific T-cell-mediated immunity, and tumour necrosis factor (TNF)-alpha activity at onset of infection. In TR mice, these responses were not precociously detected. Therefore, the absence of CD4(+) T-cell response in the first week of infection might explain the non-clearance of pathogen in TR mice. However, TR mice did show an increase in TNF level and delayed-type hypersensitivity response after the first week post-infection; there was also expansion and increase in granulomatous foci and CFU in the spleen. The expansion of granulomatous foci and the increase in TNF-alpha and tissue fungal load to damaging levels induced severe tissue destruction, general failure of the organs, cachexy and death in TR mice. The results show that genetic selection for extreme phenotypes of immunological tolerance also modified the responses to S. schenckii infection.


Assuntos
Tolerância Imunológica/genética , Sporothrix , Esporotricose/imunologia , Animais , Predisposição Genética para Doença , Hipersensibilidade Tardia/imunologia , Imunidade Celular , Interferon gama/sangue , Dose Letal Mediana , Macrófagos/imunologia , Camundongos , Ovalbumina/imunologia , Fagocitose , Seleção Genética , Sporothrix/isolamento & purificação , Esporotricose/sangue , Esporotricose/microbiologia , Fatores de Tempo , Fator de Necrose Tumoral alfa/análise
11.
Am J Respir Cell Mol Biol ; 24(5): 518-26, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11350820

RESUMO

In this study we examined the effect of oral antigen (Ag) administration on the development of experimental asthma in different mouse strains. We selected BALB/c, BP2, CBA/Ca interleukin (IL)-5 transgenic, and BALB/c T-cell receptor-delta-deficient mouse strains because they exhibit different aspects of the asthma syndrome. Mice exposed to 1% ovalbumin (OVA), dissolved in the drinking water for 5 consecutive days, became unresponsive to subsequent immunogenic OVA challenges. This regimen of OVA administration induced Ag-specific unresponsiveness in all mouse strains tested, including gammadelta-deficient mice that are said to be resistant to tolerance induction. The Ag-specific unresponsiveness was characterized by reduced (almost absent) airway eosinophilic inflammation, airway hyperreactivity, and mucus production; also by low levels of T helper (Th) 2-type cytokines in bronchoalveolar lavage fluid, and decreased immunoglobulin (Ig) G1 and IgE OVA-specific antibody production. The unresponsive state was not associated with increased levels of the suppressive cytokines IL-10 and transforming growth factor (TGF)-beta or with immune deviation toward the Th1 pathway due to increased levels of interferon-gamma and IL-12. Moreover, treatment with anti- TGF-beta antibodies did not abrogate oral tolerance. Oral Ag administration was quite effective in suppressing the development of key features of asthma when initiated after primary immunization (Day 0) or after booster (Day 7), but not after challenge (Day 14) when it increased allergic responses. Collectively, our findings show for the first time the beneficial and detrimental effects of oral Ag administration on the development of experimental asthma.


Assuntos
Asma/imunologia , Asma/terapia , Tolerância Imunológica/imunologia , Terapia de Imunossupressão/métodos , Administração por Inalação , Administração Oral , Animais , Anticorpos/sangue , Antígenos/administração & dosagem , Antígenos/imunologia , Asma/metabolismo , Asma/patologia , Testes de Provocação Brônquica , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Citocinas/metabolismo , Modelos Animais de Doenças , Esquema de Medicação , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Interleucina-5/genética , Interleucina-5/metabolismo , Camundongos , Camundongos Endogâmicos , Camundongos Transgênicos , Muco/metabolismo , Ovalbumina/administração & dosagem , Ovalbumina/imunologia , Eosinofilia Pulmonar/tratamento farmacológico , Eosinofilia Pulmonar/patologia , Receptores de Antígenos de Linfócitos T gama-delta/deficiência , Receptores de Antígenos de Linfócitos T gama-delta/genética , Células Th2/imunologia , Células Th2/metabolismo
12.
Eur J Immunol ; 30(2): 431-7, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10671198

RESUMO

The role of inflammatory and specific immune responses in pristane-induced arthritis (PIA) was investigated in mouse lines produced by bi-directional selective breedings for maximal (AIRmax) or minimal (AIRmin) acute inflammatory reaction, comparing the outcome of PIA and the humoral and cellular response to hsp65. Symptoms of arthritis were detected in 50 % AIRmax mice 120 days after pristane injection, reaching a maximal incidence of 65 %, whereas only 7 % of AIRmin mice developed arthritis within an observation period of 200 days. The production of IgG antibody against hsp65 was found to be similar on both lines, although the IgG1 isotype was predominant in AIRmax, and IgG2a in AIRmin line. In vitro T cell proliferation to hsp65 was similar in the two lines, however, ELISPOT assays carried out soon after pristane treatment, demonstrated higher numbers of IL-6-, TNF-alpha- and IL-4-secreting cells in the spleen of AIRmax than in AIRmin mice, while higher numbers of IFN-gamma-producing cells were found in AIRmin mice. These results suggest a major participation of acute inflammatory mechanisms in the susceptibility to PIA. The genetic background which determines high or low AIR favors a Th2-like response in susceptible AIRmax and Th1-like response in resistant AIRmin mice at the initial phase of arthritis induction.


Assuntos
Artrite Reumatoide/imunologia , Inflamação/imunologia , Reação de Fase Aguda/imunologia , Reação de Fase Aguda/fisiopatologia , Animais , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/fisiopatologia , Suscetibilidade a Doenças/imunologia , Imunossupressores/imunologia , Imunossupressores/toxicidade , Inflamação/fisiopatologia , Camundongos , Terpenos/imunologia , Terpenos/toxicidade
13.
Cancer Lett ; 136(2): 153-8, 1999 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-10355744

RESUMO

High and low antibody responder lines of mice from Selections I, III and G were assayed for two-step skin tumorigenesis using a protocol consisting in initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). Concordant results were obtained in the three selections: low antibody responder mice were shown to be significantly more resistant to tumor induction than the high responder counterparts. The difference was observed for all parameters: kinetics and percentages of tumor incidence and tumor multiplicity. The three bidirectional selective breeding experiments differed in several respects namely, the origin of the foundation populations, the antigens and immunization protocols used during the selection, as well as the breeding unit environments. Therefore, the consistent results relative to tumorigenesis strongly suggest that some of the alleles relevant to multispecific 'low' antibody production could contribute to the resistance to cutaneous chemical tumorigenesis.


Assuntos
Carcinógenos/toxicidade , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/imunologia , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Animais , Formação de Anticorpos , Testes de Carcinogenicidade , Suscetibilidade a Doenças/imunologia , Camundongos , Especificidade da Espécie , Acetato de Tetradecanoilforbol/toxicidade
14.
Eur J Obstet Gynecol Reprod Biol ; 83(1): 77-9, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10221614

RESUMO

OBJECTIVE: The aim of this study was to evaluate the production of tumor necrosis factor (TNF) by peripheral blood cells during pregnancy, at the onset of labor and of spontaneous abortion (SA), as well as in non-pregnant women with and without a history of recurrent spontaneous abortions (RSA). STUDY DESIGN: The peripheral blood cells TNF production was evaluated in 28 women in the 1st trimester of pregnancy, 21 in the 2nd, and 30 in the 3rd, 47 at term labor; 43, at the onset of SA; 19 healthy and 19 RSA non-pregnant women. The statistical method used was the Mann-Whitney test. RESULTS: We observed (1) lack of TNF detection in the 1st gestational trimester; (2) increase of TNF production with gestational age, with the highest values being observed at labor (P<0.05); (3) high TNF production at the onset of SA; (4) no difference in the TNF production by healthy and RSA non-pregnant women. CONCLUSIONS: The suppression of TNF production during the 1st trimester of pregnancy seems to favor the normal development of pregnancy. It remains to be investigated whether the assessment of TNF production is a valuable prognostic parameter for the occurrence of abortion.


Assuntos
Aborto Espontâneo/sangue , Início do Trabalho de Parto/sangue , Gravidez/sangue , Fator de Necrose Tumoral alfa/biossíntese , Feminino , Idade Gestacional , Humanos , Estatísticas não Paramétricas
15.
Eur J Immunol ; 28(9): 2913-20, 1998 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9754578

RESUMO

The intensity of nonspecific immune reaction and the host resistance to facultative intracellular pathogens are found to be associated in lines of mice selected for maximal (AIRmax) or minimal (AIRmin) acute inflammatory reactivity. AIRmax are more resistant than AIRmin mice to Salmonella typhimurium and Listeria monocytogenes infection, the differences between lines in LD50 being > 1000 and 100 times, respectively. This difference was shown to be related to the initial bacterial containment at the infectious focus, and to the control of bacterial multiplication in the spleen during the 1st week after s. c. inoculation of the bacteria. Specific immune responses were not deeply affected by the selective process: antibody production and delayed-type hypersensitivity were both of similar intensity in AIRmax and AIRmin mice. The differential susceptibility to infection seems independent of the Nramp-1 locus polymorphism; therefore, these two lines represent a powerful model for investigating the role of other genetic loci regulating the nonspecific immunity effectors in the course of infectious diseases.


Assuntos
Reação de Fase Aguda/imunologia , Proteínas de Transporte/genética , Proteínas de Transporte de Cátions , Predisposição Genética para Doença , Imunidade Inata/genética , Listeriose/imunologia , Proteínas de Membrana/genética , Salmonelose Animal/imunologia , Reação de Fase Aguda/genética , Alelos , Animais , Proteínas de Transporte/imunologia , Proteínas de Membrana/imunologia , Camundongos , Polimorfismo Genético , Especificidade da Espécie
16.
Eur. j. immunol ; 28(9): 2913-2930, 1998.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP, SESSP-IBACERVO | ID: biblio-1062756

RESUMO

The intensity of nonspecific immune reaction and the host resistance to facultative intracellular pathogens are found to be associated in lines of mice selected for maximal (AIRmax) or minimal (AIRmin) acute inflammatory reactivity. AIRmax are more resistant than AIRmin mice to Salmonella typhimurium and Listeria monocytogenes infection, the differences between lines in LD50 being > 1000 and 100 times, respectively. This difference was shown to be related to the initial bacterial containment at the infectious focus, and to the control of bacterial multiplication in the spleen during the 1st week after s. c. inoculation of the bacteria. Specific immune responses were not deeply affected by the selective process: antibody production and delayed-type hypersensitivity were both of similar intensity in AIRmax and AIRmin mice. The differential susceptibility to infection seems independent of the Nramp-1 locus polymorphism; therefore, these two lines represent a powerful model for investigating the role of other genetic loci regulating the nonspecific immunity effectors in the course of infectious diseases.


Assuntos
Animais , Cobaias , Ratos , Listeria monocytogenes , Salmonella typhimurium , Autoimunidade , Inflamação
17.
Immunology ; 75(1): 80-5, 1992 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-1371495

RESUMO

T-helper function was evaluated in mice genetically selected for high (H) or low (L) antibody (Ab) responsiveness to Salmonella flagellar antigen (Ag) (Selection III). In this Selection as opposed to what was demonstrated in Selections I, II and IVA, the interline difference was not proven to be based upon the modification of Ag processing and presentation at macrophage level. CD4+/CD8+ lymph node ratio is similar in HIII and LIII mice, both lines being equally susceptible to in vivo depletion of CD4+ T cells by GK 1-5 monoclonal antibody (mAb) treatment. Nevertheless, the Ab responsiveness of the two lines was differently modulated by GK 1-5 mAb: the inhibition of Ab responses to various Ag required lower mAb doses and was long lasting in LIII as compared to the transient effect of higher mAb doses observed in HIII. LIII mice were also refractory to Salmonella-induced reversion of GK 1-5 mAb inhibition. Moreover, in vitro specific I proliferation was constantly lower in LIII, though its IL-2 production was unexpectedly similar to that of HIII T cells. Results of in vivo and in vitro experiments are thus consistent with a defective response of T-helper cells to immunogenic challenge in LIII mice.


Assuntos
Antígenos CD4/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Anticorpos Monoclonais/imunologia , Formação de Anticorpos/imunologia , Divisão Celular/imunologia , Feminino , Interleucina-2/biossíntese , Linfonodos/imunologia , Ativação Linfocitária/imunologia , Masculino , Camundongos , Camundongos Endogâmicos , gama-Globulinas/imunologia
18.
Ann Inst Pasteur Immunol ; 138(3): 359-70, 1987.
Artigo em Inglês | MEDLINE | ID: mdl-3651239

RESUMO

The high (H) and low (L) antibody responder lines of mice produced by selective breeding are characterized by different modifications in immunocompetent cell potentialities, according to the immunization procedure used for the selection process. In selections I and II, the difference in antibody responsiveness between H and L lines was clearly shown to depend mainly on macrophage function: the more rapid catabolism of antigens in L mice was the main cause of the low antibody production. In contrast, up to now, no difference has been observed between H and L mice of selections III and IV in terms of the macrophage accessory role. The administration of silica particles has a well known impairment effect on macrophage activity. Therefore, the effect of silica injection on the kinetics of antibody responses to selection antigens was compared in H and L mice of the four selections. Silica was given either intravenously or locally in one hind footpad 6 or 24 h before immunization by the same route. Silica treatment consistently improved antibody responsiveness in the L mice of selections I and II, but had no effect in the L mice of selections III and IV. The antibody responses of the H lines of the four selections were not substantially modified by silica injections. Therefore, the silica treatment reduced the interline difference in antibody responses in selections I and II only, by interfering with the expression of the genetic modification of macrophage activity. However, a similar effect was not obtained with other substances known to affect macrophages, including dextran sulphate or carrageenan. The results reported here are in agreement with the above-mentioned statement that the genetic modification of macrophage function plays a major role in the interline difference in selections I and II and is not involved in selections III and IV.


Assuntos
Formação de Anticorpos/efeitos dos fármacos , Animais , Antígenos/administração & dosagem , Eritrócitos/imunologia , Regulação da Expressão Gênica/efeitos dos fármacos , Imunização , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos
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