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
K Hymes, M Nardi, A Leaf and S Karpatkin
Department of Medicine, NYU Medical Center, NY.
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.
Volume 81,
Issue 9,
pp. 2375-2380,
05/01/1993
Copyright © 1993 by The American Society of Hematology
