Platelet-activating factor enhances complement-dependent phagocytosis of diamide-treated erythrocytes by human monocytes through activation of protein kinase C and phosphorylation of complement receptor type one (CR1).
Oligomerization of band 3 protein has been recently indicated as an early event in senescent or damaged red cell membrane followed by specific deposition of anti-band 3 antibodies and binding of complement C3 fragments. The band 3-anti-band 3-C3b complex is recognized by homologous monocytes, and phagocytosis ensues. This study shows that recognition of the anti-band 3-C3b complex by the monocyte C3b receptor type one (CR1) plays a crucial role in the process of removal of damaged red cells. Indeed, blocking of monocyte CR1 with an anti-CR1 monoclonal antibody abrogated phagocytosis of diamide-treated red cells. Platelet-activating factor (PAF) is a phospholipid mediator involved in inflammatory processes. Nanomolar (R)-PAF enhanced the CR1-dependent phagocytosis of diamide-treated human red cell and of sheep red cells coated with C3b, induced the fast translocation of protein kinase C to monocyte membrane compartment, and stimulated the phosphorylation of monocyte CR1. The biologically inert lyso-PAF and the enantiomer (S)-PAF were inactive. PAF receptor antagonists and inhibitors of protein kinase C blocked the enhancement of phagocytosis induced by PAF. Protein kinase C translocation, phosphorylation of CR1, and stimulation of this receptor to an active state capable of mediating phagocytosis represent a novel pathway by which PAF interferes with red cell homeostasis and possibly modulates inflammatory reactions and host mechanisms against infections.
Bussolino
F
F
Dipartimento di Genetica, Universitá di Torino, Italy.
Fischer
E
E
Turrini
F
F
Kazatchkine
M D
MD
Arese
P
P
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D001391:Azo Compounds / Q000494:pharmacology*; D002448:Cell Adhesion; D003165:Complement System Proteins / Q000502:physiology*; D003958:Diamide / Q000494:pharmacology*; D004789:Enzyme Activation; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D010172:Palmitoylcarnitine / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects*; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000097:blood*; D011951:Receptors, Complement / Q000378:metabolism*; D013110:Sphingosine / Q000494:pharmacology; D019311:Staurosporine; D013329:Structure-Activity Relationship
D000470:Alkaloids; D001391:Azo Compounds; D007546:Isoquinolines; D010879:Piperazines; D010972:Platelet Activating Factor; D011951:Receptors, Complement; D003958:Diamide; D010172:Palmitoylcarnitine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D003165:Complement System Proteins; D011493:Protein Kinase C; D019311:Staurosporine; D013110:Sphingosine