TY - JOUR
T1 - Blood cell-derived tissue factor influences host response during murine endotoxemia
AU - Schoenmakers, Saskia H. H. F.
AU - Groot, Angelique P.
AU - Florquin, Sandrine
AU - Reitsma, Pieter H.
AU - Spek, C. Arnold
PY - 2004
Y1 - 2004
N2 - During endotoxemia, blood coagulation becomes activated due to tissue factor (TF) expression on leukocytes and/or endothelial cells. We investigated the influence of blood cell-derived tissue factor on murine endotoxemia. Therefore, we generated mice that lack tissue factor on their blood cells by transplanting tissue factor-deficient hematopoietic stem cells into lethally irradiated wild-type recipients. Control mice were also irradiated but were injected with stem cells from wild-type littermate embryos. Seven weeks after transplantation, the mice received 250 mug of endotoxin intraperitoneally. Three hours later, the mice were bled and plasma and organs were collected to assess inflammation, coagulation, and apoptosis. Mice that lack tissue factor on their blood cells still reacted to endotoxemia, but markedly less than wild-type controls. Blood cell-derived tissue factor-deficient mice showed significantly less clinical symptoms than control mice. Levels of circulating inflammatory mediators and thrombin-antithrombin (TAT) complexes were lower in blood cell-derived tissue factor-deficient mice than in controls. Surprisingly, inflammation was seen more often in blood cell-derived tissue factor-deficient mice than in control mice, but signs of apoptosis were more pronounced in controls. In summary, our data clearly indicate that endotoxin-induced coagulation and inflammation are strongly influenced by blood cell-derived tissue factor. (C) 2004 Elsevier Inc. All rights reserved
AB - During endotoxemia, blood coagulation becomes activated due to tissue factor (TF) expression on leukocytes and/or endothelial cells. We investigated the influence of blood cell-derived tissue factor on murine endotoxemia. Therefore, we generated mice that lack tissue factor on their blood cells by transplanting tissue factor-deficient hematopoietic stem cells into lethally irradiated wild-type recipients. Control mice were also irradiated but were injected with stem cells from wild-type littermate embryos. Seven weeks after transplantation, the mice received 250 mug of endotoxin intraperitoneally. Three hours later, the mice were bled and plasma and organs were collected to assess inflammation, coagulation, and apoptosis. Mice that lack tissue factor on their blood cells still reacted to endotoxemia, but markedly less than wild-type controls. Blood cell-derived tissue factor-deficient mice showed significantly less clinical symptoms than control mice. Levels of circulating inflammatory mediators and thrombin-antithrombin (TAT) complexes were lower in blood cell-derived tissue factor-deficient mice than in controls. Surprisingly, inflammation was seen more often in blood cell-derived tissue factor-deficient mice than in control mice, but signs of apoptosis were more pronounced in controls. In summary, our data clearly indicate that endotoxin-induced coagulation and inflammation are strongly influenced by blood cell-derived tissue factor. (C) 2004 Elsevier Inc. All rights reserved
U2 - https://doi.org/10.1016/j.bcmd.2003.12.002
DO - https://doi.org/10.1016/j.bcmd.2003.12.002
M3 - Article
C2 - 15003826
SN - 1079-9796
VL - 32
SP - 325
EP - 333
JO - Blood cells, molecules & diseases
JF - Blood cells, molecules & diseases
IS - 2
ER -