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International Immunology, Vol. 11, No. 2, 217-227, February 1999
© 1999 Japanese Society for Immunology

Mechanisms of acute inflammatory lung injury induced by abdominal sepsis

Brigitte Neumann1,2, Niko Zantl1, Andreas Veihelmann3, Klaus Emmanuilidis1, Klaus Pfeffer2, Claus-Dieter Heidecke1 and Bernhard Holzmann1,2

1 Department of Surgery, Klinikum rechts der Isar, Technical University, 81675 Munich, Germany
2 Institute for Medical Microbiology, Immunology and Hygiene, Technical University, 81675 Munich, Germany
3 Department of Orthopedic Surgery, Klinikum Grosshadern, Ludwig Maximilian University, 81377 Munich, Germany

Correspondence to: B. Holzmann, Department of Surgery, Klinikum rechts der Isar, Technische Universität, Ismaninger Strasse 22, 81675 Munich, Germany

Sequestration of neutrophils and release of histotoxic mediators are considered important for the development of pathologic alterations of the lung defined as adult respiratory distress syndrome. Mechanisms of inflammatory lung injury caused by abdominal sepsis were investigated using the colon ascendens stent peritonitis (CASP) model that closely mimics the human disease. In the CASP model, a continuous leakage of intraluminal bacteria into the peritoneal cavity is induced by implantation of a stent in the ascending colon, generating a septic focus. In contrast to the cecal ligation and puncture model of peritonitis, survival of mice following CASP surgery is dependent on IFN-{gamma}, but independent of tumor necrosis factor (TNF). Here we show that the systemic inflammation induced by CASP surgery results in a rapid and profound increase of lung vascular permeability that was associated with the activation and recruitment of neutrophils to the lung. Activation of circulating granulocytes was characterized by increased production of serine proteinases and reactive oxygen metabolites, as well as elevated expression of cell surface Mac-1. Expression of MIP-2, KC, MIP-1{alpha} and E-selectin mRNA in lung was strongly increased within 3 h following CASP surgery, whereas up-regulation of IP-10, MCP-1 and P-selectin was delayed. In contrast, induction of RANTES, LIX, ICAM-1 and VCAM-1 mRNA was weak or not detectable after CASP surgery. Importantly, recruitment of leukocytes to the lung was normal in lipopolysaccharide-resistant mice, and was not affected by antibody neutralization of TNF or the chemokines MIP-2 and KC.

Keywords: cell adhesion molecules, chemokines, IFN-{gamma}, KC, MIP-2, neutrophil activation, sepsis animal models, tumor necrosis factor-{alpha}

Transmitting editor: I. L. Weissman


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