Tissue factor (TF) is a transmembrane
protein, which is essential for initiation of the coagulation cascade. TF has been reported to play an important role in the progression of
endotoxin (
lipopolysaccharide, LPS)-mediated
endotoxemia, being induced in numerous tissues, such as kidney, spleen and lung. We developed and validated a rabbit anti-
murine TF peptide antiserum to localize TF
protein in a murine
sepsis model. TF
protein distribution was compared to localization of TF
mRNA and
fibrin deposits, the ultimate resultant of procoagulant TF activity. Evident LPS mediated TF
mRNA induction was observed in the tubular area at the cortico-medullar junction in the kidney, and TF activity was increased after 6 hours of
endotoxemia. In the spleen, however, TF
mRNA was induced in the interfollicular region upon LPS injection, corresponding to increased TF
protein in the same area. The clusters of TF-
protein positive cells in the spleen are predominantly granulocytes, but no TF
mRNA expression was observed within these cells. Based on these observations and the presence of TF-
protein positive granulocytes after
splenectomy, we hypothesize that granulocytes take-up TF for transport to other locations in order to initiate
fibrin formation or to induce pro-inflammatory gene expression upon interaction with
factor VIIa.