Fibronectin degradation products containing the cytoadhesive tetrapeptide stimulate human neutrophil degranulation

J Clin Invest. 1988 May;81(5):1310-6. doi: 10.1172/JCI113456.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Monoclonal
  • Cytoplasmic Granules / metabolism
  • Fibrinolysin / metabolism
  • Fibronectins / metabolism*
  • Fibronectins / pharmacology
  • Humans
  • Neutrophils / metabolism*
  • Neutrophils / ultrastructure
  • Oligopeptides / pharmacology*
  • Pancreatic Elastase / metabolism
  • Peptide Fragments / metabolism*

Substances

  • Antibodies, Monoclonal
  • Fibronectins
  • Oligopeptides
  • Peptide Fragments
  • arginyl-glycyl-aspartyl-serine
  • Pancreatic Elastase
  • Fibrinolysin