Expression of LFA-1 adhesion molecules on cisplatin-treated macrophages.
Appropriately activated mononuclear phagocytes mediate contact-dependent tumoricidal activity. Adhesion structures involved in contact-dependent tumor cytotoxicity have not been defined. The present study was aimed at identifying the adhesion structure involved in the tumoricidal activity of cisplatin-activated murine peritoneal macrophages. Tumor cells of different histological origin were used as targets in a 24-h cytotoxicity assay. Anti-CD18 (LFA-1 beta) substantially inhibited macrophage cytotoxicity whereas anti-LFA-1 alpha marginally inhibited macrophage-mediated cytotoxicity. When combined together, almost complete inhibition of tumoricidal activity was observed. Activated macrophages showed augmented binding to target cells and anti-LFA MAb inhibited the binding of resting and activated macrophages to target cells. Cisplatin augmented the expression of LFA-1 alpha and beta integrins and LPS had no effect as assessed by immunoprecipitation. These results implicate that in cisplatin activated macrophages LFA-1 alpha and beta integrins are important molecules in contact-dependent tumoricidal activity.
Shrivastava
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School of Biotechnology, Banaras Hindu University, Varanasi, India.
Shishodia
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Sodhi
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002945:Cisplatin / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D005260:Female; D005347:Fibroblasts; D007375:Interleukin-1 / Q000096:biosynthesis; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis* / Q000187:drug effects* / Q000276:immunology; D008223:Lymphoma; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D008297:Male; D012515:Mast-Cell Sarcoma; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D016169:Lymphocyte Function-Associated Antigen-1; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D002945:Cisplatin