Regulation by protein kinase of phagocytosis of Mycobacterium leprae by macrophages.
Mycobacterium leprae multiplies within host macrophages. The mechanism of internalisation of the bacteria by the phagocytic cells is unknown. In this study, M. leprae was purified from the foot pads of experimentally infected nu/nu mice. Peritoneal macrophages were harvested from BALB/c mice or C57 beige (bg/bg) mice. The effect of protein kinase inhibitors (erbstatin, genistein or staurosporine for BALB/c and bg/bg mice, plus herbimycin for bg/bg mice) on phagocytosis of the mycobacteria by the macrophage monolayers was tested. The untreated (control) macrophages phagocytosed M. leprae. Phagocytosis by BALB/c macrophages was inhibited by erbstatin and staurosporine but not by genistein; all the protein kinase inhibitors prevented uptake of M. leprae by bg/bg cells. The results demonstrate that protein kinase regulates phagocytosis of M. leprae by macrophages. The mechanism might prove to be a rational drug target for mycobacteria that multiply intracellularly.
Prabhakaran
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US Public Health Service, GWL Hansen's Disease Center @ Louisiana State University, PO Box 25072, Baton Rouge, LA 70894-5072, USA.
Harris
E B
EB
US Public Health Service, GWL Hansen's Disease Center @ Louisiana State University, PO Box 25072, Baton Rouge, LA 70894-5072, USA.
Randhawa
B
B
US Public Health Service, GWL Hansen's Disease Center @ Louisiana State University, PO Box 25072, Baton Rouge, LA 70894-5072, USA.
D000818:Animals; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006873:Hydroquinones / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009166:Mycobacterium leprae / Q000276:immunology*; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D006873:Hydroquinones; D047428:Protein Kinase Inhibitors; D019833:Genistein; D011494:Protein Kinases; D019311:Staurosporine; C048212:erbstatin