RESUMO
1. The effects of deltamethrin on mouse bone marrow and spleen progenitor cell responsiveness to granulocyte and macrophage colony-stimulating factors (CSFs) were evaluated. 2. Deltamethrin (1-5 mg/kg) was administered four times subcutaneously on alternate days for one week to male BALB/c mice, 5-8 weeks old (N = 6 mice/group), raised under pathogen-free conditions and maintained in conventional animal rooms for four weeks before use. Soft agar colony formation (CFU-C), marrow and spleen cell counts as well as body, spleen and thymus weights were determined. 3. Although treatment with the lowest dose (1 mg kg-1 48 h-1) produced no significant effect on CFU-C, the administration of 3 and 5 mg kg-1 48 h-1 caused a more than two-fold increase in the formation of granulocyte and macrophage colonies in the marrow, but not in the spleen (control value = 100.5 +/- 12 for N = 6). Colony numbers returned to normal values within five days after the end of deltamethrin administration. 4. No changes were observed in the total (range: 1-3 x 10(8) per spleen) and differential marrow and spleen cell counts, nor was there any alteration in spleen weight. However, treatment with the three doses resulted in a dramatic reduction in thymus weight. 5. These effects were not due to the liberation of endotoxin, because if endotoxin had been present it would have been < 0.060 ng/ml, a concentration that would not have a biological effect. 6. In vitro addition of 0.10 to 10 microM deltamethrin to marrow cell cultures obtained from untreated mice did not induce any response. 7. These data indicate that the CSF-driven granulocyte and macrophage development provides a useful model for the study of the effects of toxicants on myelopoiesis.
Assuntos
Células da Medula Óssea , Células-Tronco Hematopoéticas/efeitos dos fármacos , Piretrinas/toxicidade , Baço/citologia , Animais , Medula Óssea/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/efeitos dos fármacos , Fator Estimulador de Colônias de Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Nitrilas , Tamanho do Órgão/efeitos dos fármacos , Piretrinas/administração & dosagem , Baço/efeitos dos fármacosRESUMO
Las señales positivas y negativas juegan un papel trascendental en la regulación del sistema hematopoyético. En los últimos 30 años se purificaron más de 20 moléculas (glicoproteínas) con actividad biológica sobre las células progenitoras del sistema hematopoyético y sobre las células maduras circulantes. Los factores de crecimiento hematopoyéticos son las más conocidas de estas biomoléculas (citocinas como los factores estimulantes de colonias y las interleucinas), las cuales son capaces de estimular a las células de la médula ósea para producir descendencia madura. Hasta el presente se ha podido determianr no sólo la secuencia de la mayoría de estas glicoproteínas y los gene que las codifican, sino también caracterizar a las células blanco de cada uno de los factores y a sus receptores celulares. Los estudios de la interacción entre las células progenitoras hematopoyéticas y los factores que estimulan y/o inhiben su proliferación, han demostrado ser muy útiles en el desarrollo de terapias clínicas y podrían ser herramientas importantes en el análisis de la patogenia de muchas enfermedades hematológicas. Sin embargo, los mecanismos subyacentes en la producción de factores estimulantes o inhibidores y la proliferación de las células progenitoras hematopoyéticas continúan siendo escasamente conocidos (AU)
Assuntos
Humanos , Hematopoese/efeitos dos fármacos , Glicoproteínas/farmacologia , Células-Tronco Hematopoéticas/fisiologia , Fator Estimulador de Colônias de Macrófagos/efeitos dos fármacos , Receptores de Fator Estimulador de Colônias/fisiologiaRESUMO
Positive and negative signals are crucial in the regulation of the hematopoietic system. In the last 30 years, more than 20 molecules (glycoproteins) with biological activity upon the hematopoietic progenitor cells and even on the mature blood cells have been purified. The best known of these biomolecules are the hematopoietic growth factors (colony stimulating factors and interleukins), which are able to stimulate bone marrow cells to give mature progeny. At present, not only the sequence of the majority of these glycoproteins and their codifying genes has been determined, but also their target cells and cellular receptors. Research studies of the interaction between the hematopoietic progenitor cells and their stimulating and inhibiting factors are very helpful in the development of clinical trials and have become important tools to explore the origin of a great number of hematological diseases. However, the mechanisms underlying growth/inhibitory factor production and progenitor cell proliferation remain poorly understood.