Fibronectin degradation products containing the cytoadhesive tetrapeptide stimulate human neutrophil degranulation.
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.
Wachtfogel
Y T
YT
Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Abrams
W
W
Kucich
U
U
Weinbaum
G
G
Schapira
M
M
Colman
R W
RW
D000911:Antibodies, Monoclonal; D003594:Cytoplasmic Granules / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D009504:Neutrophils / Q000378:metabolism* / Q000648:ultrastructure; D009842:Oligopeptides / Q000494:pharmacology*; D010196:Pancreatic Elastase / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D005353:Fibronectins; D009842:Oligopeptides; D010446:Peptide Fragments; C046617:arginyl-glycyl-aspartyl-serine; D010196:Pancreatic Elastase; D005341:Fibrinolysin