Alteration of macrophage differentiation into accessory and effector cells from exposure to dimethylnitrosamine (DMN) in vivo.
DMN exposure modulates cellular immunity through alterations in the maturation and hematopoiesis of macrophages. DMN-exposed bone marrow stem cells gave rise to increased colony-forming unit-macrophage (CFU-M) colonies while the resulting colonies produced fewer cells/colony. Bone marrow-derived macrophages phenotypically had decreased cells expressing Ia antigens or cells in the S-phase following DMN treatment. Concanavalin A-elicited peritoneal exudate cells from DMN-treated animals demonstrated an increase in the percentage of macrophages and in the number of immature, bi-nucleated cells obtained as well as a concomitant increase in the percentage of Ia antigen-expressing cells. Concanavalin A-elicited peritoneal exudate cells from DMN-exposed animals also had an increased secreted interleukin-1 activity following lipopolysaccharide stimulation without any alteration in the expression of membrane-bound interleukin-1. Thioglycolate-elicited peritoneal exudate cells from DMN-exposed animals demonstrated no changes in cellularity and only showed increases in the percentage of bi-nucleated cells. There were no alterations in the capacity of T cells obtained from DMN-treated animals to respond to either soluble (keyhole limpet hemocyanin) or allo-antigens; nor were there alterations in the capacity of these T cells to either produce or respond to interleukin-2. These findings suggest that the observed DMN-induced modulation(s) in cell-mediated immunity results from changes in macrophage hematopoiesis due to alterations in: the production of regulatory factors controlling their production and/or differentiation or their ability to respond to these factors.
D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects; D004128:Dimethylnitrosamine / Q000494:pharmacology*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007111:Immunity, Cellular / Q000187:drug effects; D007375:Interleukin-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007377:Interleukin-3 / Q000096:biosynthesis; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D007376:Interleukin-2; D007377:Interleukin-3; D004128:Dimethylnitrosamine