RESUMEN
Exposure to nicotine during intrauterine development leads to immunodeficiency manifested in inhibition of delayed-type hypersensitivity reaction and reduced number of antibody-producing cells forming in response to sheep erythrocytes in newborn mice. The number of splenic CFU in the bone marrow of newborn mice exposed to nicotine in utero is decreased compared to the control. By contrast, nicotine induced an increase in splenic CFU count in fetal liver. We concluded that nicotine modifying the hemopoietic microenvironment delayed the release of primitive precursors from fetal liver, which impaired colonization of fetal bone marrow and led to imbalance in the production of mature blood cell, including immune system cells.
Asunto(s)
Feto/efectos de los fármacos , Sistema Inmunológico/efectos de los fármacos , Sistema Inmunológico/embriología , Intercambio Materno-Fetal , Nicotina/farmacología , Animales , Animales Recién Nacidos , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/inmunología , Ensayo de Unidades Formadoras de Colonias , Cruzamientos Genéticos , Femenino , Feto/citología , Hipersensibilidad Tardía , Hígado/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , EmbarazoRESUMEN
A biological function of endogenously expressed MuLV p15E-related proteins for lymphocyte and hematopoietic precursor activity in mice was examined. A high level of endogenous p15E-related peptide expression in spleen cells of mice with hemolytic anemia rendered by phenylhydrazine (PHZ) treatment was observed, detected by hyperimmune rabbit antisera against amino acid sequence which compose the immunosuppressive domain (ISD) of exogenous viral transmembrane (TM) p15E protein. The conditioned medium of these cultured cells (PHZ/CM) was inhibitory for lymphocyte blastogenesis and granulocyte-macrophage (GM) precursor activity, but stimulatory for the erythroid colony growth. When added to PHZ/CM, anti-ISD/p15E antibodies were capable to abrogate these effects. These antibodies bound 14K and 48K structural peptides contented in PHZ/CM as presumably smaller components of env gene products. Given together, the results indicate that erythroid immature cells produce proteins appearing in cell culture medium which exert p15E-related properties. These peptides are suggested to exert a down regulation for both lymphocyte and GM precursor activities, and the colony-promoting effect towards erythroid compartment cells.
Asunto(s)
Células Madre Hematopoyéticas/metabolismo , Linfocitos/metabolismo , Retroviridae , Proteínas del Envoltorio Viral/metabolismo , Animales , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Fenilhidrazinas/farmacologíaRESUMEN
A possible biologic activity of endogenously expressed env sequence of retroviral mink cell focus-forming virus (MCF) genome for hematopoietic colony formation was studied in mice. Antisense 20-mer complementary to MCF env sequence was used to detect the result of blockage of this gene translation on the potency of marrow cells to form colonies of erythroid (BFU-E), myeloid granulocyte-macrophage (CFU-GM), and stem cell (day 11 CFU-S) hematopoietic compartments. A large relative decrease in BFU-E number was found in bone marrow cell cultures preincubated with antisense oligonucleotide during 4 h, whereas CFU-GM colonies remained unaffected. A marked reduction of CFU-S colony formation was also registered under antisense oligomer influence. Following a decreased proliferation of erythroid progenitors, we suggest the mechanism by which antisense oligonucleotide could cause the loss of colony formation. Taken together, these data allow to propose that the expression of this gene is naturally significant for hematopoietic progenitor activity exerting some property of env gene products to regulate the growth of erythroid and multilineage hematopoietic precursors.
Asunto(s)
Genes env , Células Madre Hematopoyéticas/efectos de los fármacos , Virus Inductores de Focos en Células del Visón/genética , Oligonucleótidos Antisentido/farmacología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , División Celular/efectos de los fármacos , Células Cultivadas , Ensayo de Unidades Formadoras de Colonias , Células Madre Hematopoyéticas/citología , Masculino , Ratones , Ratones Endogámicos C57BL , Datos de Secuencia Molecular , Oligonucleótidos Antisentido/genéticaRESUMEN
The retroviral transmembrane p15E peptide is known to suppress a wide variety of immune cell functions, suggesting a role for immunosuppression associated with retroviral infection. The 10-amino acid sequence from the highly conserved portion of p15E (CKS-10) is capable of reproducing this inhibitory activity. In this study we set out to determine the influence of this decapeptide on murine spleen cell mitogen-induced proliferation and hematopoietic granulocyte-macrophage and erythroid precursor colony formation in vitro. A dose- and time-dependent suppression of spleen cell blastogenic response was produced by the CKS-10 peptide. When bone marrow cells were incubated with decapeptide, the significant decrease of CFU-GM colony number was also dose-dependent. In contrast, the same doses of CKS-10 peptide which induced a most significant inhibition of CFU-GM colony formation caused a marked increase of BFU-E colonies. A most pronounced effect of the peptide on bone marrow hematopoietic progenitor activity was produced by prolonged exposure to the peptide. Given the results of this study, it seems likely that, in addition to the cytopathic effect of retroviruses on the lymphocytes, viral peptide-mediated hematopoiesis disorders may also play an important role in the pathogenesis of immunodeficiency associated with retroviral infections.