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Neutrophil cathepsin G modulates the platelet surface expression of the
glycoprotein (GP) Ib-IX complex by proteolysis of the von Willebrand factor
binding site on GPIb alpha and by a cytoskeletal-mediated redistribution of
the remainder of the complex
CA LaRosa, MJ Rohrer, SE Benoit, MR Barnard and AD Michelson
Division of Vascular Surgery, University of Massachusetts Medical School,
Worcester 01655.
The effects of neutrophil cathepsin G on the glycoprotein (GP) Ib-IX
complex of washed platelets were examined. Cathepsin G resulted in a
concentration- and time-dependent decrease in the platelet surface GPIb- IX
complex, as determined by flow cytometry, binding of exogenous von
Willebrand factor (vWF) in the presence of ristocetin, and ristocetin-
induced platelet agglutination. Cathepsin G resulted in proteolysis of the
vWF binding site on GPIb alpha (defined by monoclonal antibody [MoAb] 6D1),
as determined by increased supernatant glycocalicin fragment (a proteolytic
product of GPIb alpha); decreased total platelet content of GPIb; and lack
of effect of either cytochalasin B (an inhibitor of actin polymerization),
prostaglandin I2 (an inhibitor of platelet activation), or prior fixation
of the platelets. However, cathepsin G resulted in minimal decreases in the
binding to fixed platelets of MoAbs TM60 (directed against the thrombin
binding site on GPIb alpha) and WM23 (directed against the
macroglycopeptide portion of GPIb alpha). In contrast to its proteolytic
effect on GPIb alpha, the cathepsin G-induced decrease in platelet surface
GPIX and the remnant of the GPIb-IX complex (defined by MoAbs FMC25 and
AK1) was via a cytoskeletal-mediated redistribution, as determined by lack
of change in the total platelet content of GPIX and the GPIb-IX complex;
complete inhibition by cytochalasin B, prostaglandin I2, and prior fixation
of platelets. Experiments with Serratia protease-treated and Bernard-
Soulier platelets showed that neither platelet surface GPIb nor cathepsin
G-induced proteolysis of GPIb were required for the cathepsin G-induced
redistribution of the remnant of the GPIb-IX complex or the cathepsin
G-induced increase in platelet surface P-selectin. In summary, neutrophil
cathepsin G modulates the platelet surface expression of the GPIb-IX
complex both by proteolysis of the vWF binding site on GPIb alpha and by a
cytoskeletal-mediated redistribution of the remainder of the complex. Prior
studies show that, although thrombospondin 1, antiserine proteases, and
plasma are all inhibitors of cathepsin G, the effects of cathepsin G on
platelets, including an increase in surface GPIIb-IIIa, occur during close
contact between neutrophils and platelets in a protective microenvironment
(eg, thrombosis and local inflammation).(ABSTRACT TRUNCATED AT 400 WORDS)
Volume 84,
Issue 1,
pp. 158-168,
07/01/1994
Copyright © 1994 by The American Society of Hematology
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