Role of leuCAM integrins and complement in platelet-monocyte rosette formation induced by immune complexes of human immunodeficiency virus-type 1-immune thrombocytopenic purpura patients.
Patients with human immunodeficiency virus-type 1-immune thrombocytopenic purpura (HIV-1-ITP) have elevated polyethylene glycol (PEG)-precipitable immune complexes (ICs) composed of IgG, IgM, and complement that are threefold to sevenfold higher than in healthy control subjects. These complexes contain anti-F (ab')2 as well as anti-idiotype antibodies versus anti-HIV-1gp120. Because anti-F (ab')2 and anti-idiotype antibodies correlate with thrombocytopenia (r = .83 [J Clin Invest 77:1756, 1986] and r = .90 [J Clin Invest 89:356, 1992], respectively) we studied the binding of ICs to platelets and monocytes as well as their role in platelet-monocyte rosette formation. ICs bind to platelets in a saturation-dependent manner (optimum at 10 micrograms/mL; 0.5% of serum conc). Binding to platelets could not be inhibited with platelet saturating concentrations of aggregated IgG or with monoclonal antibody (MoAb) IV.3 versus FcR gamma II. Platelet binding could be inhibited with Fab anti-C3, anti-Clq, or anti-C4 by 57%, 40%, and 46% respectively, not with control Fab (P < .001). Monocytes from HIV-1-ITP patients form rosettes with normal platelets 16.8 +/- 5.2 rosettes/100 monocytes compared with 4.8 +/- 0.8 control monocytes plus normal platelets (P = .009). Gel-washed HIV-1-ITP platelets formed 19 +/- 2.0 rosettes with U937 cells compared to 6.3 +/- 1.0 for normal platelets (P = 0.001). Arming of U937 cells with HIV-1-ITP ICs (5 micrograms/mL) formed 36.7 +/- 2.5 rosettes compared with 10.6 +/- 1.2 for control ICs (P < .01). Rosetting of armed U937 cells could be inhibited with MoAbs versus the alpha chains of CD11a (LFA-1), 11b (Mac-1), or 11c (p150,95) by 67%, 70%, and 61%, respectively (P < .007), whereas binding of ICs to U937 cells was unaffected. Isotype-matched control as well as MoAbs versus antigens on U937 cells (CD13, CD33) or the anti-FcR gamma II receptor had no effect. However, Fab fragments of polyclonal anti-C3 inhibited rosette formation by 78% (P < .01); control Fab had no effect. Thus, platelet-monocyte rosette formation is not Fc dependent. It is complement receptor dependent and requires the cooperation of all three leuCAM integrins.
Hymes
K
K
Department of Medicine, NYU Medical Center, NY.
Nardi
M
M
Leaf
A
A
Karpatkin
S
S
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood* / Q000150:complications / Q000276:immunology; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex / Q000097:blood*; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology*; D003176:Complement C3 / Q000276:immunology; D003181:Complement C4 / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology; D015497:HIV-1; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D010980:Platelet Membrane Glycoproteins / Q000276:immunology* / Q000502:physiology; D011092:Polyethylene Glycols / Q000494:pharmacology; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood* / Q000209:etiology / Q000276:immunology; D012016:Reference Values; D012397:Rosette Formation; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D003176:Complement C3; D003181:Complement C4; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010980:Platelet Membrane Glycoproteins; D011092:Polyethylene Glycols; D003165:Complement System Proteins