AJP - Lung Cellular and Molecular Physiology, Vol 267, Issue 5 609-L617, Copyright © 1994 by American Physiological Society
Endotoxin responsiveness and grain dust-induced inflammation in the lower respiratory tract
D. A. Schwartz, P. S. Thorne, P. J. Jagielo, G. E. White, S. A. Bleuer and K. L. Frees
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
To identify the role of endotoxin responsiveness in grain dust-induced
airway disease, we used two models of extotoxin hyporesponsiveness to
perform inhalation exposure studies in mice. In the first model, we
investigated whether genetic resistance to endotoxin would alter the
inflammatory response to inhaled grain dust by comparing the inflammatory
response in the lower respiratory tract of endotoxin-sensitive and
-resistant male mice after inhalation of pyrogen-free saline, corn dust
extract (CDE), sterile CDE (SCDE), or lipopolysaccharide (LPS).
Endotoxin-sensitive and -resistant mice were exposed for 4 h to nebulized
solutions of LPS, SCDE, or CDE. Another group of endotoxin-sensitive and
-resistant mice was sham exposed for 4 h to nebulized sterile saline.
Dose-response relationships for endotoxin were explored for LPS, SCDE, and
CDE. Bronchoalveolar lavage (BAL) 5 h after the start of exposure
demonstrated a higher concentration of total cells, neutrophils (PMNs), and
tumor necrosis factor-alpha (TNF-alpha) in BAL fluid after inhalation of
CDE, SCDE, or LPS in endotoxin-sensitive than in endotoxin-resistant mice.
Whereas endotoxin-sensitive mice demonstrated a dose-response relationship
between the endotoxin concentration in each of the solutions and the
concentration of cells, PMNs, and TNF-alpha in BAL fluid, concentrations of
TNF-alpha were significantly higher only in BAL fluid of
endotoxin-resistant mice exposed to higher concentrations of SCDE or CDE.
In the second model, we investigated whether acquired endotoxin tolerance
would alter the inflammatory response to SCDE.(ABSTRACT TRUNCATED AT 250
WORDS)
