RESUMO
BACKGROUND: The bone marrow is considered to be an important storage of parasites in Leishmania-infected dogs, although little is known about cellular genesis in this organ during canine visceral leishmaniasis (CVL). METHODOLOGY/PRINCIPAL FINDINGS: The aim of the present study was to evaluate changes in erythropoiesis and leucopoiesis in bone marrow aspirates from dogs naturally infected with Leishmania chagasi and presenting different clinical statuses and bone marrow parasite densities. The evolution of CVL from asymptomatic to symptomatic status was accompanied by increasing parasite density in the bone marrow. The impact of bone marrow parasite density on cellularity was similar in dogs at different clinical stages, with animals in the high parasite density group. Erythroid and eosinophilic hypoplasia, proliferation of neutrophilic precursor cells and significant increases in lymphocytes and plasma cell numbers were the major alterations observed. Differential bone marrow cell counts revealed increases in the myeloid:erythroid ratio associated to increased numbers of granulopoietic cells in the different clinical groups compared with non-infected dogs. CONCLUSIONS: Analysis of the data obtained indicated that the assessment of bone marrow constitutes an additional and useful tool by which to elaborate a prognosis for CVL.
Assuntos
Células da Medula Óssea/parasitologia , Eritropoese/fisiologia , Leishmania/patogenicidade , Leishmaniose/parasitologia , Leucopoese/fisiologia , Animais , Cães , Feminino , Leishmaniose/patologia , MasculinoRESUMO
In adults, haemopoiesis is located in the bone marrow, where it is tightly regulated by cytokines and by a physical association of haemopoietic progenitors with the stroma. However, in pathological situations, haemopoiesis can be partly or fully dislodged to peripheral tissues. It is not clear which are the requirements for a given peripheral stroma to sustain haemopoiesis. Using the growth factor-dependent cell line FDC-P1, we have compared the myelopoietic capacities of a murine bone marrow-derived cell line S17, a liver inflammatory granuloma-derived stroma (GR) that sustains haemopoiesis, and normal skin fibroblasts (SF) that sustain neither survival nor proliferation of myeloid cells. All three stromas expressed mRNA for major haemopoietins with the exception of IL-3. Despite the incapacity of SF to sustain FDC-P1 cells, the biologically active GM-CSF could be recovered from all the studied stromas by treatment with high-salt buffers that release non-covalently bound molecules from stroma cells. Glycosaminoglycans purified from stromas had distinct effect on the GM-CSF-mediated proliferation of FDC-P1 cells: those purified from S17 and GR cells were stimulatory, whereas those obtained from SF cells were slightly stimulatory at low concentration, but inhibitory at the higher ones. We conclude that the quality of the stroma pericellular glycoconjugates is determinant for the ability of a given stroma to sustain myelopoiesis, even when biologically active haemopoietins are locally produced.
Assuntos
Comunicação Celular/fisiologia , Espaço Extracelular/metabolismo , Substâncias de Crescimento/metabolismo , Leucopoese/fisiologia , Células Progenitoras Mieloides/metabolismo , Células Estromais/metabolismo , Animais , Divisão Celular/fisiologia , Células Cultivadas/citologia , Células Cultivadas/metabolismo , Técnicas de Cocultura , Citocinas/genética , Citocinas/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Glicosaminoglicanos/metabolismo , Glicosaminoglicanos/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Substâncias de Crescimento/genética , Camundongos , Células Progenitoras Mieloides/citologia , Proteínas Proto-Oncogênicas c-kit/genética , RNA Mensageiro/metabolismo , Células Estromais/citologia , Radioisótopos de EnxofreRESUMO
We have examined the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in tumor-bearing BALB/c mice using the syngeneic F3II mammary carcinoma. In the present model, progression of subcutaneous tumors induced massive myelopoiesis in bone marrow and spleen due to GM-CSF secretion by tumor cells. In vitro, the addition of recombinant mouse GM-CSF (5- 25 ng/ml) caused a significant increase in F3II cell growth, either in the presence or absence of serum. Zymographic analysis of conditioned media from F3II monolayers showed that GM-CSF exerted a dose-dependent enhancement in the metalloproteinases MMP-9 (105 kD) and MMP-2 (70 kD), key enzymes in mammary tumor cell invasion. Our data suggest that ectopic GM-CSF production stimulates myelopoiesis and may also play an important role in tumor progression and metastasis formation.
Assuntos
Medula Óssea/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/fisiologia , Leucopoese , Neoplasias Mamárias Experimentais/metabolismo , Baço/metabolismo , Animais , Biomarcadores Tumorais , Divisão Celular , Relação Dose-Resposta a Droga , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Leucopoese/fisiologia , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/patologia , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Invasividade Neoplásica , Metástase Neoplásica , Células Tumorais CultivadasRESUMO
Las células del sistema inmune que incluyen linfocitos, granulocitos y monocitos-macrófagos, se forman en la médula ósea a partir de células pluripotentes, a través de un proceso finamente regulado y el que participan varias citoquinas. Los granulocitos (neutrófilos, eosinófilos y basófilos) presentan particularidades morfológicas y funcionales. La principal función de los neutrófilos es su capacidad fagocítica. En el capítulo se explican los procesos de activación, quimiotaxis, fagocitosis y bacteriolisis. Las células del sistema fagocítico mononuclear (monocitos y macrófagos) tienen como función fagocitar; actividad más desarrollada en los macrófagos, que son células tisulares derivadas de los monocitos circulantes. Los linfocitos son las células que participan en la inmunidad adquirida o específica. Las células T participan en la inmunidad celular y las células B en la inmunidad humoral. Una tercera subpoblación de linfocitos, las células NK, participan en la inmunidad celular de tipo innata. Los órganos linfoides se pueden clasificar en primarios (timo y médula ósea) y secundarios (bazo, ganglios linfáticos y tejido linfoide asociado a mucosas). En el timo maduran los LT y en la médula ósea los LB. En los órganos linfoides secundarios los linfocitos y otras células del sistema inmune toman contacto con los antígenos y es en ellos donde se genera la respuesta inmune específica. En estos órganos existen zonas ricas en células T, y otras en que, principalmente, existen células B. La capacidad de los linfocitos de recircular entre los órganos linfoides secundarios, vasos linfáticos, conducto torácico y vasos sanguíneos le permiten tomar contacto con antígenos en diferentes lugares del organismo
Assuntos
Humanos , Sistema Imunitário/anatomia & histologia , Sistema Imunitário/fisiologia , Basófilos/imunologia , Bolsa de Fabricius/imunologia , Eosinófilos/imunologia , Granulócitos/imunologia , Leucopoese/fisiologia , Tecido Linfoide/imunologia , Macrófagos/imunologia , Monócitos/imunologia , Fagócitos/imunologia , Sistema Linfático/imunologia , Timo/imunologiaRESUMO
In this work we demonstrate that the stress-induced reduction in bone marrow granulocyte-macrophage colonies, reported previously from our laboratory, is prevented by both the inhibition of the hypothalamic-pituitary-adrenal axis (HPAA) and the blockage of opioid receptors. The inhibition of the HPAA was obtained through the administration of dexamethasone (1 mg/kg). The blockage of opioid receptors was done in two ways, by the administration of naltrexone (8 mg/kg) and induction of tolerance to morphine. On the other hand, no protection was observed in metyrapone treated rats. We suggest that the two physiological systems, opioid and HPAA, mediate the stress-induced myelosuppression and that these systems may function independently in this particular situation.