Stimulus and cell-specific expression of c-x-c and c-c chemokines
by pulmonary stromal cell populations.
Lukacs, N. W., S. L. Kunkel, R. Allen, H. L. Evanoff, C. L. Shaklee,
J. S. Sherman, M. D. Burdick, and R. M. Strieter.
University of Michigan Medical School, Dept. of Pathology and
Internal Medicine; Div of Pulmonary and Critical Care, Ann Arbor,
MI.
APStracts 2:0020L, 1995.
Chronic inflammatory responses in the lung rely on the continual
recruitment of leukocytes to the site of inflammation. Recent data
has demonstrated a possible role for stromal cell-derived chemokines
in leukocyte recruitment. In the present study we examined the
production of IL-8 and ENA-78, members of the C-X-C family of
chemokines, and MIP-1 a and b, members of the C-C chemokine family,
from pulmonary smooth muscle and endothelial cells. The production of
IL-8 and ENA-78 was induced by early response cytokines, IL-1 and
TNF, but not by immune-associated cytokines, IL-4, IL-10, or IFN-g.
In contrast, the production of MIP-1 a/b by pulmonary vascular smooth
muscle cells increased when stimulated by immune-associated
cytokines, as well as with IL-1b and TNF. The level of MIP-1 a
production induced by immune-associated cytokines, IL-4, IFN-g and
IL-10. The production of MIP-1 b in response to immune-associated
cytokines, IL-4, IFN-g and IL-10. Human pulmonary artery endothelial
cells did not generate MIP-1 a or b in response to graded doses of
any of the cytokines. These data demonstrate differential induction
of C-X-C and C-C chemokines from nonimmune stromal cell populations.
The C-X-C chemokines are induced primarily by early response
cytokines, IL-1b and TNF. However, the C-C chemokines were induced in
smooth muscle cells, but not endothelial cells, by both early
response and immune-associated cytokine stimulation. These mechanisms
may be pertinent in the development and regulation of acute and
chronic inflammatory responses.
Received 1 August 1994; accepted in final form 27 December 1994.
APS Manuscript Number L217-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 February 1995.