Expression of tissue factor and interleukin-1β in a novel rabbit model of disseminated intravascular coagulation induced by carrageenan and lipopolysaccharide

Y. A. Elsayed, K. Nakagawa, K. Ichikawa, S. Ohkawara, K. Sueishi

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Abstract

Thrombus formation and the sequential expression of tissue factor (TF), interleukin-1β (IL-1β) and interleukin-1 receptor antagonist (IL-1ra) in several organs were examined immunohistochemically and morphometrically in a novel model of disseminated intravascular coagulation (DIC) developed by modifying the generalized Shwartzman reaction (GSR) in rabbits. The new model [carrageenan (CA)-lipopolysaccharide (LPS)] was induced by the administration of a priming dose of intraperitoneal CA, 10 mg/kg, followed 24 h later by a provocative dose of LPS 25 μg/kg, while GSR was induced by the intravenous injection of two doses of LPS 25 μg/kg. CA was detected predominantly within macrophages in the spleen and liver. Fibrin thrombi were formed as early as 1 h after the second LPS treatment in all examined organs reaching a peak at 3-9 h and their prevalence was higher in the CA-LPS group (p < 0.05). The sequential expressions of TF and IL-1β correlated well with each other in both groups reaching a peak at 3-9 h with the CA-LPS group showing a more pronounced expression than the GSR group. Macrophages in the liver, spleen and lungs, and Bowman's epithelial cells expressed both proteins, while IL-1β was also expressed by endothelial and epithelial cells. IL-1ra was expressed by the same cells expressing IL-1β, however, its expression continued to increase gradually over 24 h. The mortality rate was lower (p < 0.05) and neutrophilic sequestration less prominent in the CA-LPS group than in the GSR group. These findings indicate that CA efficiently replaced the priming LPS treatment and the consequently enhanced production of IL-1β may have resulted in the upregulation of TF expression leading to the high level of thrombi in this new model which may provide a tool for further studies on the role of cytokines in DIC.

Original languageEnglish
Pages (from-to)328-340
Number of pages13
JournalPathobiology
Volume63
Issue number6
DOIs
Publication statusPublished - Jan 1 1995

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All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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