Growth factors are released by mechanically wounded endothelial cells

Paul L McNeil, L. Muthukrishnan, E. Warder, P. A. D'Amore

Research output: Contribution to journalArticle

333 Citations (Scopus)

Abstract

Growth factors may be required at sites of mechanical injury and normal wear and tear in vivo, suggesting that the direct action of mechanical forces on cells could lead to growth factor release. Scraping of cells from the tissue culture substratum at 37°C was used to test this possibility. We show that scraping closely mimics in vitro both the transient plasma membrane wounds observed in cells subject to mechanical forces in vivo (McNeil, P.L., and S. Ito. 1989. Gastroenterology. 96:1238-1248) and the transient plasma membrane wounds shown here to occur in endothelial cells under normal culturing conditions. Scraping of endothelial cells from the culturing substratum released into the culture medium a potent growth-promoting activity for Swiss 3T3 fibroblasts. Growth-promoting activity was released rapidly (within 5 min) after scraping but was not subsequently degraded by the endothelial cells for at least 24 h thereafter. A greater quantity of growth-promoting activity was released by cells scraped 4 h after plating than by those scraped 4 or 7 d afterwards. Thus release is not due to scraping-induced disruption of extracellular matrix. Release was only partially cold inhibitable, was poorly correlated with the level of cell death induced by scraping, and did not occur when cells were killed with metabolic poisons. These results suggest that mechanical disruption of plasma membrane, either transient or permanent, is the essential event leading to release. A basic fibroblast growth factor-like molecule and not platelet-derived growth factor appears to be partially responsible for the growth-promoting activity. We conclude that one biologically relevant route of release of basic fibroblast growth factor, a molecule which lacks the signal peptide sequence for transport into the neoplasmic reticulum, could be directly through mechanically induced membrane disruptions of endothelial cells growing in vivo and in vitro.

Original languageEnglish (US)
Pages (from-to)811-822
Number of pages12
JournalJournal of Cell Biology
Volume109
Issue number2
DOIs
StatePublished - Jan 1 1989

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Intercellular Signaling Peptides and Proteins
Endothelial Cells
Cell Membrane
Fibroblast Growth Factor 2
Wounds and Injuries
Reticulum
Poisons
Platelet-Derived Growth Factor
Gastroenterology
Protein Sorting Signals
Tears
Extracellular Matrix
Culture Media
Cell Death
Cell Culture Techniques
Fibroblasts
Membranes
growth promoting activity
In Vitro Techniques

ASJC Scopus subject areas

  • Cell Biology

Cite this

McNeil, P. L., Muthukrishnan, L., Warder, E., & D'Amore, P. A. (1989). Growth factors are released by mechanically wounded endothelial cells. Journal of Cell Biology, 109(2), 811-822. https://doi.org/10.1083/jcb.109.2.811

Growth factors are released by mechanically wounded endothelial cells. / McNeil, Paul L; Muthukrishnan, L.; Warder, E.; D'Amore, P. A.

In: Journal of Cell Biology, Vol. 109, No. 2, 01.01.1989, p. 811-822.

Research output: Contribution to journalArticle

McNeil, PL, Muthukrishnan, L, Warder, E & D'Amore, PA 1989, 'Growth factors are released by mechanically wounded endothelial cells', Journal of Cell Biology, vol. 109, no. 2, pp. 811-822. https://doi.org/10.1083/jcb.109.2.811
McNeil, Paul L ; Muthukrishnan, L. ; Warder, E. ; D'Amore, P. A. / Growth factors are released by mechanically wounded endothelial cells. In: Journal of Cell Biology. 1989 ; Vol. 109, No. 2. pp. 811-822.
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