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

Research output: Contribution to journalArticle

71 Citations (Scopus)

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

Fingerprint

Fibronectins
Adhesives
Glycoproteins
Neutrophils
Peptide Hydrolases
Fibroblasts
Leukocytes
Proteolysis
Connective Tissue Cells
Agglutination
Cell Adhesion
Connective Tissue
Sheep
Membrane Proteins
Proteins
Collagen
Erythrocytes
Molecular Weight
Maintenance
Inflammation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Destruction of a major extracellular adhesive glycoprotein (fibronectin) of human fibroblasts by neutral proteases from polymorphonuclear leukocyte granules. / McDonald, J. A.; Baum, B. J.; Rosenberg, D. M.; Kelman, J. A.; Brin, S. C.; Crystal, Ronald.

In: Laboratory Investigation, Vol. 40, No. 3, 31.08.1979, p. 350-357.

Research output: Contribution to journalArticle

@article{b833f1c753b9435488b6711f00448c77,
title = "Destruction of a major extracellular adhesive glycoprotein (fibronectin) of human fibroblasts by neutral proteases from polymorphonuclear leukocyte granules",
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.",
author = "McDonald, {J. A.} and Baum, {B. J.} and Rosenberg, {D. M.} and Kelman, {J. A.} and Brin, {S. C.} and Ronald Crystal",
year = "1979",
month = "8",
day = "31",
language = "English",
volume = "40",
pages = "350--357",
journal = "Laboratory Investigation",
issn = "0023-6837",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - Destruction of a major extracellular adhesive glycoprotein (fibronectin) of human fibroblasts by neutral proteases from polymorphonuclear leukocyte granules

AU - McDonald, J. A.

AU - Baum, B. J.

AU - Rosenberg, D. M.

AU - Kelman, J. A.

AU - Brin, S. C.

AU - Crystal, Ronald

PY - 1979/8/31

Y1 - 1979/8/31

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0018380499&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0018380499&partnerID=8YFLogxK

M3 - Article

C2 - 423528

AN - SCOPUS:0018380499

VL - 40

SP - 350

EP - 357

JO - Laboratory Investigation

JF - Laboratory Investigation

SN - 0023-6837

IS - 3

ER -