Neutrophils express tissue factor in a monkey model of sepsis.
BACKGROUND
Although tissue factor (TF) is involved in hemostasis, thrombogenesis, inflammation, and cellular immune response, its source in sepsis remains controversial. Recently, we found that, in addition to monocytes and endothelial cells, neutrophils may express TF in a rabbit model. The purpose of this study was to determine whether neutrophils could be a source of TF in a monkey model of sepsis.


METHODS
TF messenger RNA (mRNA) and protein in neutrophils were assayed by in situ hybridization and immunohistochemistry in tissues obtained from monkeys after injection of lipopolysaccharide (LPS) (n = 3) and after injection of saline as a control (n = 2). Coagulation parameters were measured before and at 1.5 and 3 hours after injections.


RESULTS
In LPS-treated monkeys, TF mRNA and protein were induced not only in monocytes and endothelial cells, but also in neutrophils accumulating in the liver 3 hours after LPS injection. Thrombin-antithrombin III complex and fibrin degradation products D-dimer levels were significantly increased at 3 and 1.5 hours after LPS injection compared with controls.


CONCLUSIONS
Neutrophils are a source of TF and are implicated in direct activation of the coagulation cascade in the early phases of sepsis in the monkey. These results give important information for the treatment of sepsis.
Todoroki
H
H
Department of Surgery 1, University of Occupational and Environmental Health, Kitakyushu, Japan.
Nakamura
S
S
Higure
A
A
Okamoto
K
K
Takeda
S
S
Nagata
N
N
Itoh
H
H
Ohsato
K
K
D000818:Animals; D000990:Antithrombin III / Q000032:analysis; D004926:Escherichia coli; D005337:Fibrin / Q000032:analysis; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008070:Lipopolysaccharides; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008168:Lung / Q000737:chemistry / Q000473:pathology; D008251:Macaca; D008253:Macaca mulatta; D008297:Male; D009504:Neutrophils / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D018805:Sepsis / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D013925:Thromboplastin / Q000096:biosynthesis*
D005338:Fibrin Fibrinogen Degradation Products; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D005337:Fibrin; D013925:Thromboplastin; D010447:Peptide Hydrolases