RGD Reference Report - Mechanisms of acute inflammatory lung injury induced by abdominal sepsis. - Rat Genome Database

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Mechanisms of acute inflammatory lung injury induced by abdominal sepsis.

Authors: Neumann, B  Zantl, N  Veihelmann, A  Emmanuilidis, K  Pfeffer, K  Heidecke, CD  Holzmann, B 
Citation: Neumann B, etal., Int Immunol. 1999 Feb;11(2):217-27.
RGD ID: 5135253
Pubmed: PMID:10069420   (View Abstract at PubMed)

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-1alpha 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Acute Lung Injury  ISOCxcl1 (Mus musculus)5135253; 5135253associated with Sepsis and mRNA:increased expression:lungRGD 
Acute Lung Injury  ISOCxcl2 (Mus musculus)5135253; 5135253associated with Sepsis and mRNA:increased expression:lungRGD 
Acute Lung Injury  IEP 5135253; 5135253associated with Sepsis and mRNA:increased expression:lungRGD 

Objects Annotated

Genes (Rattus norvegicus)
Cxcl1  (C-X-C motif chemokine ligand 1)
Cxcl2  (C-X-C motif chemokine ligand 2)

Genes (Mus musculus)
Cxcl1  (C-X-C motif chemokine ligand 1)
Cxcl2  (C-X-C motif chemokine ligand 2)

Genes (Homo sapiens)
CXCL1  (C-X-C motif chemokine ligand 1)
CXCL2  (C-X-C motif chemokine ligand 2)


Additional Information