LFA-1-dependent tumoricidal activity of cisplatin-treated macrophages.
The role of leucocyte function associated antigen-1 (LFA-1) (CD11a/18) in the tumoricidal activity of cisplatin-treated macrophages was investigated. Anti-LFA-1 antibodies inhibited cisplatin-induced macrophage cytotoxicity towards three different tumour cell lines. The decrease in tumoricidal activity of cisplatin-treated macrophages was attributed to their decreased binding to tumour cells in the presence of anti-LFA-1 (CD11a/18) antibodies. Western blot analysis revealed that cisplatin treatment leads to the expression of LFA-1 on macrophages which otherwise remains non-detectable. Because there is no information regarding the mechanism of cisplatin-induced LFA-1 expression and tumour cell binding by macrophages, the role of various second messenger molecules in these processes was investigated. Results suggest that protein phosphatase 2A (PP2A) is not involved in these processes whereas protein tyrosine phosphatases (PTP) negatively regulate LFA-1 expression and tumour-cell binding of cisplatin-treated macrophages. Inhibitors of protein phosphatase 1 (PP1), protein kinase C (PKC), protein tyrosine kinase (PTK), calmodulin and calmodulin-dependent kinase-II (CamK II) prevented LFA-1 expression on cisplatin-treated macrophages. A comparison with earlier results indicated that LFA-expression follows a distinct signalling pathway which is separate from the signalling pathway involved in NO or tumour necrosis factor/interleukin-1 (TNF/IL-1) expression in cisplatin-stimulated macrophages.
School of Biotechnology, Banaras Hindu University, Varanasi, India.
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Singh
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Sodhi
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D007375:Interleukin-1 / Q000096:biosynthesis; D007739:L Cells; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D002147:Calmodulin; D007375:Interleukin-1; D016169:Lymphocyte Function-Associated Antigen-1; D014409:Tumor Necrosis Factor-alpha; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2; D017027:Protein Tyrosine Phosphatases; D002945:Cisplatin; D002118:Calcium