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Expression of platelet C1 inhibitor
AH Schmaier, S Amenta, T Xiong, GD Heda and AM Gewirtz
Department of Internal Medicine, University of Michigan, Ann Arbor.
Human platelets contain a pool of C1 inhibitor (C1 INH) distinct from that
in plasma. Twelve normal platelet samples washed by centrifugation had a
mean platelet C1 INH antigen level of 19.3 +/- 2.8 ng (mean +/- SEM) per
10(8) platelets. These values contrast with the mean +/- SEM platelet C1
INH antigen level of 6.1 +/- 0.9 per 10(8) platelets from 12 C1
INH-deficient patients. The level of platelet C1 INH correlated (r = .7)
with the level of plasma C1 INH in normal individuals and patients with
classic hereditary angioedema. Platelet C1 INH, like plasma C1 INH, was a
105-Kd protein on immunoblots of solubilized platelets and in thrombin- or
collagen-induced platelet releasates. On indirect immunofluorescence,
morphologically and immunochemically identifiable elutriated human
megakaryocytes had C1 INH antigen. Using nested primer polymerase chain
reaction, C1 INH mRNA was detected in megakaryocytes. When activated, human
platelets expressed a portion of their total pool of C1 INH antigen on
their membrane. Using a competitive enzyme-linked immunosorbent assay for
C1 INH as a quantitative, indirect antibody consumption assay, the surface
of unstimulated platelets had 0.55 +/- 0.4 ng C1 INH/10(8) platelets (mean
+/- SEM). When activated with thrombin, platelets secreted 7.37 +/- 2.2 ng
C1 INH/10(8) platelets into the suspension buffer and simultaneously
expressed 4.4 +/- 1.2 ng C1 INH/10(8) platelets on their external membrane.
These studies showed that activated platelets secreted 38% of their C1 INH
and externalized another 23% of the total platelet C1 INH on their
membrane. Furthermore, in 125I-anti-C1 INH Fab' binding experiments to
platelets, about 8 ng of the antibody fragment specifically bound to 10(8)
activated platelets. These data suggest that level of platelet C1 INH
packaged into platelet alpha-granules is modulated by the amount of protein
produced in megakaryocytes. Platelet alpha-granule C1 INH can both be
secreted from platelets and expressed on their activated membranes. The
cell membrane expression of C1 INH may be important to modulate the
activity of the proteases of the complement and contact systems of plasma
proteolysis in the microenvironment of the inflammatory response.
Volume 82,
Issue 2,
pp. 465-474,
07/15/1993
Copyright © 1993 by The American Society of Hematology

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