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Delayed inflammatory responses to endotoxin in fibrinogen‐deficient mice
Author(s) -
CruzTopete D,
Iwaki T,
Ploplis VA,
Castellino FJ
Publication year - 2006
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2060
Subject(s) - fibrinogen , inflammation , lipopolysaccharide , fibrin , immunology , medicine , pathological , tumor necrosis factor alpha , endocrinology
Abstract Severe inflammation leads to haemostatic abnormalities, such as the development of microvascular thrombi. As a result, ischaemia‐related downstream organ damage can occur. The present study demonstrates that mice with a total deficiency of fibrinogen ( Fg −/− ) present with altered responses to challenge with Gram‐negative lipopolysaccharide (LPS). Early survival in response to continuous LPS challenge was increased in Fg −/− mice and histological findings indicated that this improvement correlated with a lack of fibrin deposition in organs. Neutrophils appeared early in the lungs of challenged wild‐type (WT) mice, but occurred in Fg −/− mice at later times. This delayed response in Fg −/− mice was confirmed by studies that showed a strong dependence on Fg of binding of neutrophils to endothelial cells in the presence of LPS. While cytokines were also elevated in both WT and Fg −/− mice, their levels were generally lower at early times in this latter group. The time course of MIP‐2 expression correlated with the occurrence of pulmonary leakage after LPS challenge, which was delayed in Fg −/− mice. These results suggest that fibrin(ogen) plays a role as an early mediator in the cross‐talk between coagulation and inflammation. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.