Summary
The effect of human neutrophil elastase (HNE) on the structure and receptor activity
of platelet glycoprotein IIb/IIIa complex was studied. Resting platelets, which bound
only traces of 125I-fibrinogen in the absence of ADR were found to be barely susceptible to HNE. As
shown by immunoblotting experiments, treatment of such platelets with HNE (14 μg/ml)
did not provoke a detectable cleavage of GPIIb but resulted in a partial digestion
of GPIIIa and appearance of 110 kDa fragment. Such proteolytic modification of the
GPIIb/IIIa complex was accompanied by a slight increase in the binding of fibrinogen
to blood platelets in the absence of ADP. Treatment of partially activated platelets
(spontaneous activation during washing procedure) with HNE caused a progressive loss
of GPIIb and degradation of GPIIIa to 110 kDa and 60 kDa fragments. These spontaneously
stimulated platelets had initially a high number of fibrinogen binding sites exposed,
corresponding to approximately 50% of receptor capacity observed in platelets activated
by the optimal concentration of ADP. Digestion of GPIIb/IIIa by HNE of such platelets
markedly increased the exposure of fibrinogen receptors. Thus, the stimulation of
platelets increases significantly the susceptibility of the GPIIb/IIIa complex to
proteolysis by HNE. However, such modification of the GPIIb/IIIa does not destroy
its function as a receptor for fibrinogen either on the resting or activated platelets.
