Macrophages stimulated by receptor-ligand interactions exhibit differences in cell-cycle kinetics during tumor growth: stimulation at Mac-1 and Mac-3 receptors alters DNA synthesis.
Phenotypic and functional changes associated with tumor-bearing host (TBH) macrophages (M phi) are partly responsible for immunosuppression during tumor growth. Flow cytofluorometric analyses revealed differences in cell-cycle kinetics between normal host (NH) and TBH M phi that were stimulated at specific receptors. Receptor-ligand interactions were induced by antibodies against Mac-1, -2, -3, and Ia receptors and changes in DNA synthesis were measured over a 12-h time course by incorporation of propidium iodide. TBH M phi showed higher DNA synthesis than NH M phi over this time course irrespective of the receptor induced. NH M phi stimulated at the Mac-1 receptor demonstrated higher DNA synthesis than control NH M phi although TBH M phi stimulated at this receptor and control TBH M phi failed to show any differences. Both NH and TBH M phi exhibited small, short-term decreases in DNA synthesis when stimulated at the Mac-2 receptor. TBH M phi that were stimulated at the Mac-3 receptor demonstrated higher DNA synthesis than their control counterparts while NH M phi stimulated at this receptor and control NH M phi showed identical levels of DNA synthesis. No differences in DNA synthesis were found among normal or TBH M phi that were stimulated through Ia. Differences in DNA synthesis did not appear to be attributable to differences in receptor expression. Further analysis of Mac-1 and Mac-3 stimulated cells revealed that DNA synthesis in NH M phi stimulated at the Mac-1 receptor returned to control levels at 48 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Walker
T M
TM
Department of Biology, Virginia Polytechnic Institute and State University, Blacksburg 24061-0406.
Yurochko
A D
AD
Burger
C J
CJ
Elgert
K D
KD
D000818:Animals; D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000276:immunology*; D002453:Cell Cycle / Q000276:immunology; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D005354:Fibrosarcoma / Q000276:immunology* / Q000473:pathology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D008024:Ligands; D008262:Macrophage Activation / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011971:Receptors, Immunologic; D013778:Tetrazolium Salts; D013844:Thiazoles
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D004273:DNA, Neoplasm; D008024:Ligands; D016177:Macrophage-1 Antigen; D011971:Receptors, Immunologic; D013778:Tetrazolium Salts; D013844:Thiazoles; C036763:monocyte-macrophage differentiation antigen; C022616:thiazolyl blue