Destruction of a major extracellular adhesive glycoprotein (fibronectin) of human fibroblasts by neutral proteases from polymorphonuclear leukocyte granules

J. A. McDonald, B. J. Baum, D. M. Rosenberg, J. A. Kelman, S. C. Brin, Ronald Crystal

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Abstract

Recent evidence suggests that fibronectin, an adhesive major cell surface protein of cultured fibroblasts and a component of normal human connective tissue, is important in maintenance of normal cell to cell and cell to connective tissue relationships. We have investigated the hypothesis that fibronectin is a sensitive target of products released from normal human fibroblasts and incubated with human polymorphonuclear leukocyte granule contents under physiologic conditions. Fibronectin exposed to neutral proteases present in leukocyte granules lost its characteristic biologic properties of promoting cell adhesion to a collagen substrate and agglutination of sheep red blood cells. Electrophoretic analysis revealed that extensive proteolysis accompanied this loss of biologic activity. When the total extracellular proteins secreted by fibroblasts were exposed to leukocyte granule contents, fibronectin was more sensitive to proteolysis than the majority of other extracellular proteins. Moreover, the fibrillar network of extracellular high molecular weight cell surface fibronectin was as sensitive to proteolysis by leukocyte granule contents as was purified fibronectin. These findings demonstrate that fibronectin is a sensitive target of leukocyte proteases under physiologic conditions. Inasmuch as proteases contained in leukocyte granules are released into the surrounding milieu following appropriate physiologic stimulation, some of the changes occurring in normal tissue architecture accompanying inflammation may reflect loss of normal cell to cell and cell to connective tissue matrix interactions mediated by this adhesive cell surface molecule.

Original languageEnglish
Pages (from-to)350-357
Number of pages8
JournalLaboratory Investigation
Volume40
Issue number3
Publication statusPublished - 31 Aug 1979
Externally publishedYes

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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