Grain dust-induced lung inflammation is reduced by Rhodobacter sphaeroides diphosphoryl lipid A.
Jagielo-PJ; Quinn-TJ; Qureshi-N; Schwartz-DA
Am J Physiol, Lung Cell Mol Physiol 1998 Jan; 274(1):L26-L31
The effect of diphosphoryl-lipid-A obtained from the lipopolysaccharide (LPS) of Rhodobacter-sphaeroides (RsDPLA) on grain dust induced lung inflammation was examined. Male C3Heb/FeJ- mice intratracheally instilled with 10 micrograms (microg) of RsDPLA or saline were exposed via inhalation to LPS and corn dust extract (CDE) aerosols for 4 hours. The animals were sacrificed after exposure and lung lavage cells were isolated. In the in-vitro study, THP1 cells, a human monocytic leukemia cell line, were incubated with RsDPLA concentrations of 100 micrograms per milliliter (microg/ml) in the presence or absence of an LPS or CDE concentration of 0.02microg/ml for 24 hours. Cytokine concentrations in the human and murine cells were determined via enzyme linked immunosorbent assays. RsDPLA concentrations of 0.001 to 10microg/ml had little to no effect on tumor-necrosis-factor- alpha (TNF-alpha) release from THP1 cells. However, a RsDPLA concentration of 100microg/ml caused a significant increase in the TNF-alpha concentration. In contrast, LPS stimulated TNF-alpha release at relatively low concentrations. The increase in TNF-alpha release induced by LPS and CDE was inhibited in a dose dependent fashion by treatment with 0.001 to 1.0microg/ml RsDPLA. The inhibitory effect of RsDPLA was not evident at a concentration of 100microg/ml. Inhalation of LPS or CDE in mice caused increased total cell and neutrophil recruitment and elevated cytokine concentrations. Pretreatment with RsDPLA significantly inhibited total cell and neutrophil recruitment and significantly reduced cytokine concentrations. The authors conclude that RsDPLA, a relatively nontoxic agent, suppresses grain dust induced lung inflammation both in-vitro and in-vivo.
NIOSH-Publication; NIOSH-Grant; Pulmonary-system-disorders; Laboratory-animals; Cell-cultures; Grain-dusts; Endotoxins; Exposure-levels; Dose-response; Lung-irritants; In-vivo-study; In-vitro-study; Immunochemistry; Inhalation-studies;
Author Keywords: endotoxin; lipopolysaccharide inhibition; asthma
Paul J. Jagielo, Department of Internal Medicine, The University of Iowa College of Medicine, Iowa City, Iowa 52242-1081
American Journal of Physiology: Lung Cellular and Molecular Physiology
Internal Medicine University of Iowa 200 Hawkins Drive Iowa City, IA 52242-1081