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NEUTROPHILS PLAY A CRITICAL ROLE IN THE DEVELOPMENT OF LPS-INDUCED AIRWAY DISEASE
Citation:
Savov, J. D., S H. Gavett, D. M. Brass, D L. Costa, AND D. A. Schwartz. NEUTROPHILS PLAY A CRITICAL ROLE IN THE DEVELOPMENT OF LPS-INDUCED AIRWAY DISEASE. AMERICAN JOURNAL PHYSIOLOGICAL LUNG CELL MOLECULAR PHYSIOLOGY 283(5):L-952-L-962, (2002).
Description:
ETD-02-045 (GAVETT) GPRA # 10108
Neutrophils Play a Critical Role in the Development of LPS-Induced Airway Disease.
Jordan D. Savov, Stephen H. Gavett*, David M. Brass, Daniel L. Costa*, and David A. Schwartz
ABSTRACT
We investigated the role of neutrophils in the development of endotoxin-induced airway disease by systemic neutrophil depletion of C3H/HeBFeJ mice and coincident inhalation challenge with lipopolysaccharide (LPS) over a 4-wk period. Mice were made neutropenic with intraperitoneal injections of neutrophil antiserum started prior to and continued throughout the exposure period. Our experiment included: LPS-exposed, antiserum-treated; LPS-exposed, control serum-treated; air-exposed, antiserum-treated; and air-exposed, control serum-treated groups. Physiologic, biologic and morphologic assessments were performed following a 4-wk exposure and again following a 4-wk recovery. After the 4-wk exposure, LPS-induced inflammation of the lower airways was significantly attenuated in neutropenic mice, although without increase airway responsiveness to methacholine. Following the recovery period LPS-exposed neutrophil-replete mice had increased airway responsiveness when compared with the LPS-exposed neutropenic animals. Morphometric data indicate that the 4-wk LPS exposure results in substantial expansion of the subepithelial area of the medium size airways in nonneutropenic mice, but not in neutropenic mice ? difference, that persisted following the recovery period. Bronchial epithelial and subepithelial TGF-b1 expression was diminished in challenged neutropenic mice compared to neutrophil-sufficient mice. These studies demonstrate that neutrophils play a critical role in the development of chronic LPS-induced airway disease.