Effects of immune complex formation and complement activation on circulating platelets in the primate.

Primate platelets are different from rodent and rabbit platelets in that they do not express receptors for C3a or C5a or immune adherence receptors. This study assessed the effects of immune complex (IC)-induced complement activation on primate platelets in the circulation. Cynomolgus monkeys (CYN, N = 4) immunized to bovine gamma globulin (BGG) were infused with BGG over 5 min to induce acute intravascular IC formation and complement activation. The studies were carried out under normal complement conditions (N = 12), partial complement inhibition (CAB-2 treated, N = 3), or total complement inhibition (CVF treated, N = 1). Under normal complement conditions, BGG infusion increased C3a levels from undetectable to an average of 11.9 +/- 2.6 micrograms/ml. At this time, decreases occurring in both circulating neutrophils (85 +/- 6%) and monocytes (78 +/- 6%) were significantly greater than decreases in circulating platelets (13 +/- 3%, p < 0.001). Partial complement inhibition had an equivocal effect on the BGG-induced changes in circulating leukocytes, while total complement inhibition abrogated these changes. In contrast, platelet changes were unaffected by complement inhibition. We conclude that, compared to circulating leukocytes, circulating platelets are insensitive to intravascular complement activation induced by IC in the nonhuman primate. These results contrast with previous studies in rodents which demonstrate strong effects of IC-induced intravascular complement activation on both circulating neutrophils and platelets.

[1]  J. Köhl,et al.  Site-directed C3a receptor antibodies from phage display libraries. , 1998, Journal of immunology.

[2]  P. Higgins,et al.  A soluble chimeric complement inhibitory protein that possesses both decay-accelerating and factor I cofactor activities. , 1997, Journal of immunology.

[3]  D. Birmingham,et al.  The baboon erythrocyte complement receptor is a glycophosphatidylinositol-linked protein encoded by a homologue of the human CR1-like genetic element. , 1996, Journal of immunology.

[4]  R. Quigg,et al.  Characterization of rat complement receptors and regulatory proteins. CR2 and Crry are conserved, and the C3b receptor of neutrophils and platelets is distinct from CR1. , 1995, Journal of immunology.

[5]  W. Couser,et al.  The effects of soluble recombinant complement receptor 1 on complement-mediated experimental glomerulonephritis. , 1995, Journal of the American Society of Nephrology : JASN.

[6]  F. Cosio,et al.  Effect of chronically increased erythrocyte complement receptors on immune complex nephritis. , 1994, Kidney international.

[7]  F. Cosio,et al.  Platelet involvement in experimental immune complex-mediated glomerulonephritis in the nonhuman primate. , 1993, Kidney international.

[8]  P. Sims,et al.  The response of human platelets to activated components of the complement system. , 1991, Immunology today.

[9]  C. Alpers,et al.  Platelet-complement interactions in mesangial proliferative nephritis in the rat. , 1991, The American journal of pathology.

[10]  F. Cosio,et al.  Immune complex erythrocyte complement receptor interactions in vivo during induction of glomerulonephritis in nonhuman primates. , 1990, The Journal of laboratory and clinical medicine.

[11]  J. Koudstaal,et al.  Intraglomerular platelet aggregation and experimental glomerulonephritis. , 1990, Kidney international.

[12]  C. Alpers,et al.  Mechanisms and kinetics for platelet and neutrophil localization in immune complex nephritis. , 1989, Kidney international.

[13]  M. Casaretto,et al.  Characterization of C3a receptor‐proteins on guinea pig platelets and human polymorphonuclear leukocytes , 1989, European journal of immunology.

[14]  F. Vivanco,et al.  Role of complement-derived peptides in thrombocytopenia elicited by soluble aggregates of immunoglobulin G in the rat. , 1989, Laboratory investigation; a journal of technical methods and pathology.

[15]  K. Yancey,et al.  Analysis of the interaction of human C5a and C5a des Arg with human monocytes and neutrophils: flow cytometric and chemotaxis studies. , 1989, The Journal of investigative dermatology.

[16]  C. Alpers,et al.  Platelets mediate neutrophil-dependent immune complex nephritis in the rat. , 1988, The Journal of clinical investigation.

[17]  D. Mendrick,et al.  Determinants of immune complex-mediated glomerulonephritis. , 1988, Kidney international.

[18]  T. Hugli,et al.  Demonstration of a specific C3a receptor on guinea pig platelets. , 1988, Journal of immunology.

[19]  J. Atkinson,et al.  Identification of a C3b/iC3 binding protein of rabbit platelets and leukocytes. A CR1-like candidate for the immune adherence receptor. , 1988, Journal of immunology.

[20]  L. Cosgrove,et al.  CR3 receptor on platelets and its role in the prostaglandin metabolic pathway , 1987, Immunology and cell biology.

[21]  D. Fearon,et al.  Cellular distribution of complement receptor type 4 (CR4): expression on human platelets. , 1987, Journal of immunology.

[22]  C. Anderson,et al.  Human platelet Fc receptor for immunoglobulin G. Identification as a 40,000-molecular-weight membrane protein shared by monocytes. , 1985, The Journal of clinical investigation.

[23]  M. Polley,et al.  Human platelet activation by C3a and C3a des-arg , 1983, The Journal of experimental medicine.

[24]  P. Ward,et al.  Intravascular activation of complement and acute lung injury. Dependency on neutrophils and toxic oxygen metabolites. , 1982, The Journal of clinical investigation.

[25]  H. Jacob,et al.  Complement-induced granulocyte aggregation in vivo. , 1981, The American journal of pathology.

[26]  D. Bitter‐Suermann,et al.  Platelet-serotonin release by C3a and C5a: two independent pathways of activation. , 1981, Journal of immunology.

[27]  P. Naish,et al.  Quantitative assessment of the effects of platelet depletion in the autologous phase of nephrotoxic serum nephritis. , 1979, Clinical and experimental immunology.

[28]  D. Birmingham Erythrocyte complement receptors. , 1995, Critical reviews in immunology.

[29]  R. Frade,et al.  Activation of human platelets through gp140, the C3d/EBV receptor (CR2) , 1987, European journal of immunology.