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American Journal of Respiratory Cell and Molecular Biology. Vol. 29, pp. 432-438, 2003
© 2003 American Thoracic Society
DOI: 10.1165/rcmb.2002-0145OC

Murine Complement Interactions with Pseudomonas aeruginosa and Their Consequences During Pneumonia

John G. Younger, Sunita Shankar-Sinha, Marc Mickiewicz, Adam S. Brinkman, Gabriel A. Valencia, J. Vidya Sarma, Ellen M. Younkin, Theodore J. Standiford, Firas S. Zetoune and Peter A. Ward

Departments of Emergency Medicine and Pathology and the Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan

Address correspondence to: John G. Younger, MD, MS, 7679 Kresge Research Building I, 200 Zina Pitcher Place, Ann Arbor, MI 48109-0303. E-mail: jyounger{at}umich.edu

Complement is necessary for defense against lung infection with Pseudomonas aeruginosa in mice. We studied in vitro interactions between complement and P. aeruginosa and in vivo effects of complement depletion to better understand this relationship. In vitro, P. aeruginosa strain UI-18 was resistant to killing by mouse serum. However, C3 opsonized the organism (via the alternative and mannose binding lectin [MBL] pathways), and C5 convertase activity on the bacterial surface was demonstrated. In vivo, compared with normal mice, complement-deficient mice experienced higher mortality and failed to sterilize their bronchoalveolar space within 24 h of inoculation. These changes did not seem to be a result of decreased inflammation because complement-deficient mice had normal neutrophil recruitment, greater lung myeloperoxidase content, and, by 24 h, a 35-fold higher level of the CXC chemokine KC. Lung static pressure-volume curves were abnormal in infected animals but were significantly more so in complement deficient mice. These data indicate that although P. aeruginosa is resistant to serum killing, C3 opsonization and C5 convertase assembly occur on its surface. This interaction in vivo plays a central role in host survival beyond just recruitment and activation of phagocytes and may serve to limit the inflammatory response to and tissue injury resulting from bacterial infection.

Abbreviations: analysis of variance, ANOVA • bronchoalveolar lavage, BAL • bronchoalveolar lavage fluid, BALF • cobra venom factor, CVF • N-acetyl glucosamine, GluNAc • horseradish peroxidase, HRP • myeloperoxidase, MPO • phosphate-buffered saline, PBS




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