The role of endotoxin in grain dust induced lung inflammation in
mice.
Jagielo, Paul J., Peter S. Thorne, Jeffery A. Kern, Timothy J. Quinn,
David A. Schwartz.
Departments of Internal Medicine and Preventive Medicine and
Environmental Health, The University of Iowa College of Medicine and
the Department of Veterans Affairs, Iowa City, Iowa
APStracts 3:0020L, 1996.
To investigate the role of endotoxin in grain dust induced airway
inflammation, we reduced the endotoxin activity from extracts of corn
dust (CDE), using three distinct methods, and determined the effect
of endotoxin activity on the in vitro and in vivo inflammatory
response to CDE. E. coli lipopolysaccharide solution (LPS) and CDE
solution were separated into into greater than 100 kilodalton
(>100 kd) and less than 100 kilodalton (<100 kd) fractions
by ultracentrifugation. Endotoxin activity was predominantly present
in the >100 kd fractions of the LPS and CDE solutions. Charged
membrane filtration of the >100 kd fractions of LPS and CDE
resulted in the reduction of endotoxin activity by 99.9% and 80%,
respectively. Treatment of the >100 kd fractions of LPS and CDE
with polymyxin B coated beads reduced the endotoxin activity by 96%
and 89%, respectively. The untreated >100 kd fractions of LPS
and CDE caused significantly greater (p<0.01) release of
TNF[alpha] from THP-1 cells in vitro in comparison to its respective
<100 kd fraction or either of the treated (charged filter or
polymyxin B) >100 kd fractions. Similarly, mice exposed to
either of the untreated >100 kd fractions of LPS or CDE by
inhalation developed significantly greater (p<0.01)
concentrations of lavage neutrophils and TNF[alpha] in the lavage
fluid in comparison to mice exposed to the respective <100 kd
fraction or either of the treated >100 kd fractions. These
results indicate that endotoxin is primarily responsible for the in
vitro and in vivo inflammatory response to CDE.
Received 3 May 1995; accepted in final form 5 January 1996.
APS Manuscript Number L131-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 February 96