A possible role for granulocyte macrophage-colony stimulating factor in modulating teratogen-induced effects.
It was already shown that stimulation of the maternal immune system by allogeneic or xenogeneic leukocytes is capable of affecting embryonic responses to teratogenic insults and various cytokines, including granulocyte macrophage-colony stimulating factor (GM-CSF), were implicated as mediators of this effect. Therefore, in the present study we tried to assess the ability of GM-CSF to modulate teratogenic activity, along with possible changes in systemic as well as local maternal immune responses, that might be involved in the process. Thus, the percentage of cyclophosphamide (CP)-treated embryos exhibiting limb malformations was shown to decrease significantly following GM-CSF administration. This effect was found to be comparable to that demonstrated by intrauterine leukocytes administration. GM-CSF treatment resulted in a significant enhancement in maternal splenocytes Con-A-induced proliferation, as well as Interleukin-2 (IL-2) and IL-3 production. Examination of leukocyte cell surface antigens expressed by splenocytes revealed no statistically-significant changes in the level of the T lymphoid antigens Thy-1, CD5, CD4, CD8 and CD3, the macrophage antigen Mac-1, and the adhesion molecules LFA-1alpha, LFA-1beta and L-Selectin, following GM-CSF immunostimulation. In parallel, immunohistochemical analysis of the uteroplacental unit revealed Mac-1 and to a lesser extent LFA-1beta-positive cells localized to the myometrium and the placenta in both the control and the GM-CSF-treated groups, while no cells expressing Thy-1, CD3, CD4, CD8, or LFA-1alpha could be demonstrated. Our results suggest a possible role for GM-CSF in modulating teratogen-induced effects, a process in which maternal immune responses such as splenocytes proliferation and cytokine production might be involved.
Savion
S
S
Department of Embryology and Teratology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel. shoshans@plato.tau.ac.il
Brengauz-Breitmann
M
M
Torchinsky
A
A
Toder
V
V
D000014:Abnormalities, Drug-Induced / Q000517:prevention & control*; D000818:Animals; D002460:Cell Line; D003520:Cyclophosphamide / Q000633:toxicity*; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010920:Placenta / Q000276:immunology; D011247:Pregnancy; D051381:Rats; D020318:Rats, Long-Evans; D013154:Spleen / Q000276:immunology; D013723:Teratogens / Q000633:toxicity*; D014599:Uterus / Q000276:immunology
D013723:Teratogens; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide