You are here:
EFFECTS OF SYSTEMIC NEUTROPHIL DEPLETION ON LPS-INDUCED AIRWAY DISEASE
Citation:
Savov, J. D., S H. Gavett, D. M. Brass, D L. Costa, AND D. A. Schwartz. EFFECTS OF SYSTEMIC NEUTROPHIL DEPLETION ON LPS-INDUCED AIRWAY DISEASE. Presented at American Thoracic Society, Atlanta, GA, May 17-22, 2002.
Description:
Effects of Systemic Neutrophil Depletion on LPS-induced Airway Disease
Jordan D. Savov, Stephen H. Gavett*, David M. Brass, Daniel L. Costa*, David A. Schwartz
Pulmonary and Critical Care Division, Dept of Medicine ? Duke University Medical Center
* National Health and Environmental Effects Research Lab, US EPA, Research Triangle Park
The role of neutrophils in endotoxin-induced lung injury was evaluated by systemic neutrophil depletion of C3H/HeBFeJ mice and exposure for 4 wk to lipopolysaccharide (LPS) aerosol. Mice were made neutropenic with i.p. injection of anti-neutrophil serum prior to and 3 times per week throughout exposure to LPS or filtered air. Age-matched controls were injected with control serum. Physiologic, biologic and morphologic assessments were performed 12 hr, 3 d, and 4 wk following exposure. Twelve hr and 3 d after exposure all experimental groups of mice had equal airway responsiveness to methacholine. However 4 wk after exposure LPS-exposed control mice had increased airway responsiveness when compared with corresponding neutropenic animals. LPS caused inflammation of the lower airways 72 hr after exposure (neutrophilic bronchiolitis and alveolitis); this response was significantly attenuated in neutropenic mice. Morphometric data indicate that 4-wk LPS exposure results in substantial expansion of subepithelial area of the medium size airways (d = 90-129 m) in control mice, but not in neutropenic mice. This difference persisted following the recovery period. Immunohistochemical analysis of TGF-b1 localization indicates diminished expression of this growth factor in the epithelial and subepithelial airway layers in challenged neutropenic mice compared to neutrophil-sufficient ones. These studies demonstrate that neutrophils are essential for the development of chronic LPS-induced airway disease that includes persistent airway hyperresponsiveness and airway remodeling. (This abstract does not reflect EPA policy.)
NIEHS - ES06537, ES07498, and ES09607; NHLBI - HL62628