title: Alteration of macrophage differentiation into accessory and effector cells from exposure to dimethylnitrosamine (DMN) in vivo.
abstract: 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.
mesh_terms: 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
chemical_list: D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D007376:Interleukin-2; D007377:Interleukin-3; D004128:Dimethylnitrosamine