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Usage Information

Fibronectin degradation products containing the cytoadhesive tetrapeptide stimulate human neutrophil degranulation.
Y T Wachtfogel, … , M Schapira, R W Colman
Y T Wachtfogel, … , M Schapira, R W Colman
Published May 1, 1988
Citation Information: J Clin Invest. 1988;81(5):1310-1316. https://doi.org/10.1172/JCI113456.
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Research Article

Fibronectin degradation products containing the cytoadhesive tetrapeptide stimulate human neutrophil degranulation.

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Abstract

We investigated whether adhesive glycoproteins, such as fibronectin or fibrinogen, could function to provide a nidus for neutrophil degranulation. Elastase release in recalcified plasma was normal in afibrinogenemic plasma, but 73% less in plasma depleted of fibronectin. Proteolytic digests of fibronectin, but not intact fibronectin (50-1,000 micrograms/ml), induced a concentration-dependent release of neutrophil elastase and lactoferrin. MAbs N293, which recognized the mid-molecule of fibronectin, N294, which was directed toward the 11-kD cell adhesive fragment, and N295, generated against the amino terminal of the 11-kD fragment, inhibited the release of elastase by 7, 24, and 60%, respectively. The cytoadhesive tetrapeptide portion of fibronectin, Arg-Gly-Asp-Ser (250-1,000 micrograms/ml), released 1.94 +/- 0.10 micrograms/ml of elastase from 10(7) neutrophils, in contrast to the lack of release by the control hexapeptide, Arg-Gly-Tyr-Ser-Leu-Gly. Plasmin appeared to be the enzyme responsible for fibronectin cleavage, since neutrophil elastase release in plasma that had been depleted of plasminogen was decreased and reconstitution of plasminogen-deficient plasma with purified plasminogen corrected the abnormal release. Plasmin cleaved fibronectin to multiple degradation products, each less than 200 kD. This fibronectin digest released 1.05 microgram/ml of elastase from 10(7) neutrophils. We suggest that the activation of plasminogen leads to the formation of fibronectin degradation products capable of functioning as agonists for neutrophils.

Authors

Y T Wachtfogel, W Abrams, U Kucich, G Weinbaum, M Schapira, R W Colman

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