AJP - Lung Cellular and Molecular Physiology, Vol 257, Issue 2 65-L70, Copyright © 1989 by American Physiological Society
Endotoxin stimulates platelet-derived growth factor production from cultured human pulmonary endothelial cells
S. M. Albelda, J. A. Elias, E. M. Levine and J. A. Kern
Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia 19104.
The interaction of Gram-negative bacterial cell wall products (endotoxins)
with endothelial cells is thought to be responsible for many of the
damaging manifestations of Gram-negative sepsis. Because cultured human
endothelial cells are relatively resistant to the direct cytotoxic actions
of endotoxin, it is possible that many of the systemic effects of endotoxin
may be caused by stimulation of endothelial cells to produce biologically
active mediators which could then act on targets such as smooth muscle
cells, fibroblasts, and leukocytes. We hypothesized that one such
endothelial cell-derived mediator could be platelet-derived growth factor
(PDGF), a protein that causes proliferation of mesenchymal cells,
chemotaxis of leukocytes, fibroblasts and smooth muscle cells, and
vasoconstriction. We therefore examined the effect of endotoxin on
PDGF-like protein production by cultured adult human pulmonary artery
endothelial cells. Twenty-four hours of endotoxin exposure resulted in a
threefold increase in the steady-state levels of mRNA coding for PDGF
B-chain (c-sis) and a two- to threefold increase in the amount of newly
synthesized PDGF released into the media, as measured by
immunoprecipitation of [35S]methionine-labeled protein with anti-PDGF
antiserum. We conclude that human pulmonary artery endothelial cells in
culture are stimulated both to produce increased amounts of PDGF mRNA and
to release PDGF-like protein after exposure to endotoxin. This increased
release of PDGF-like protein by human endothelial cells may play a role in
the inflammatory infiltrate, vasospasm, and fibroblast proliferation that
characterize the host response to endotoxin.
