Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.37 (neutrophil elastase)
 4,078 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 ADP, were found to be barely susceptible to HNE. As shown by immunoblotting experiments, treatment of such platelets with HNE (14 micrograms/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.
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PMID:Different effects of human neutrophil elastase on platelet glycoproteins IIb and IIIa of resting and stimulated platelets. 227 28

We have examined the interaction of human granulocyte elastase with human platelets. Incubation of human platelets with human granulocyte elastase exposed active fibrinogen-binding sites as evidenced by 125I-labeled fibrinogen binding and spontaneous fibrinogen-induced platelet aggregation. The aggregation of platelets by fibrinogen occurred at low concentrations of human granulocyte elastase (0.5-1 microgram/ml). Platelets pretreated with human granulocyte elastase exposed an average of 10,500 fibrinogen binding sites per platelet, i.e., about one-third the number of binding sites exposed by optimal concentrations of ADP. With the use of a polyclonal antiplatelet membrane antibody, the glycoproteins IIb (GPIIb), IIIa (GPIIIa), and a 60,000-Da (60 kDa) protein (66 kDa in a reduced system) derived from GPIIIa were immunoprecipitated from the surface of detergent extracts of human 125I-radiolabeled platelets pretreated with increasing concentrations of human granulocyte elastase. Experiments performed by immunoblotting with use of polyclonal and monoclonal antibodies directed to GPIIIa showed that pretreatment of human platelets with granulocyte elastase resulted in the appearance of an additional proteolytic derivative of GPIIIa migrating with an apparent molecular mass of 120 kDa in a nonreduced system. GPIIIa appears to be the preferred substrate of elastase, since GPIIb was not degraded by human granulocyte elastase. We conclude that 1) the proteolytic action of human granulocyte elastase on platelet GPIIIa results in the formation of two major hydrolytic products, and 2) human granulocyte elastase exposes active fibrinogen-binding sites associated with the GPIIb/GPIIIa complex, resulting in direct platelet aggregation by fibrinogen.
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PMID:Granulocyte-platelet interactions and platelet fibrinogen receptor exposure. 341 26

Extramedullary hematopoiesis occurring in the myocardium has previously only been reported in a single case of a neonate with cyanotic congenital heart disease. Herein we report the incidental discovery of extramedullary hematopoiesis or pure erythropoiesis in four failing adult hearts with myocardial infarction. In two cases, extramedullary hematopoiesis or erythropoiesis was identified in cardiectomy specimens removed at orthotopic heart transplantation; in two other cases, erythropoiesis was found in left ventricular tissue removed at the time of implantation of left ventricular assist devices. Myocardial hematopoiesis/erythropoiesis was identified based on characteristic light-microscopic findings in routinely processed tissue and was confirmed by immunhistochemistry using monoclonal antibodies to the erythroid cell marker glycophorin A (positive in all cases), the megakaryocyte marker CD61, and the granulocyte marker neutrophil elastase (the latter two markers positive in one case only). None of the four patients had a myeloproliferative disorder or evidence of a myelophthisic process. No hematopoietic elements were identified in 109 cardiectomy specimens without acute or recent infarcts. Myocardial hematopoiesis or erythropoiesis could represent heretofore-unrecognized manifestations of altered cytokine expression in patients with heart failure due to myocardial infarction.
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PMID:Hematopoiesis/erythropoiesis in myocardial infarcts. 1140 61