Phagocytosis by macrophages mediated by receptors for denatured proteins - dependence on tyrosine protein kinases.
Previous studies have demonstrated that some components of the leukocyte cell membrane, CR3 (Mac-1, CD11b/CD18) and p150/95, are able to bind to denatured proteins. Thus, it is of interest to know which effector functions of these cells can be triggered by these receptors when they interact with particles or surfaces covered with denatured proteins. In the present study we analyzed their possible role as mediators of phagocytosis of red cells covered with denatured bovine serum albumin (BSA) by mouse peritoneal macrophages. We observed that a) macrophages are able to recognize (bind to) these red cells, b) this interaction can be inhibited by denatured BSA in the fluid phase, c) there is no phagocytosis of these particles by normal macrophages, d) phagocytosis mediated by denatured BSA can be, however, effectively triggered in inflammatory macrophages induced by glycogen or in macrophages activated in vivo with LPS, and e) this phagocytic capacity is strongly dependent on the activity of tyrosine protein kinases in its signal transduction pathway, as demonstrated by using three kinds of enzyme inhibitors (genistein, quercetin and herbimycin A).
Hespanhol
M R
MR
Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
Mantovani
B
B
D000818:Animals; D002417:Cattle; D004912:Erythrocytes / Q000502:physiology; D006003:Glycogen / Q000378:metabolism; D008264:Macrophages / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis / Q000502:physiology*; D011489:Protein Denaturation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism; D012756:Sheep; D015398:Signal Transduction
D012709:Serum Albumin; D006003:Glycogen; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases