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Effect of human urinary thrombomodulin on endotoxin‐induced intravascular coagulation and pulmonary vascular injury in rats
Author(s) -
Uchiba Mitsuhiro,
Okajima Kenji,
Murakami Kazunori,
Johno Masayoshi,
Okabe Hiroaki,
Takatsuki Kiyoshi
Publication year - 1997
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/(sici)1096-8652(199702)54:2<118::aid-ajh4>3.0.co;2-#
Subject(s) - thrombomodulin , disseminated intravascular coagulation , ards , medicine , sepsis , pulmonary edema , thrombin , coagulation , lung , respiratory distress , pharmacology , immunology , pathology , anesthesia , platelet
Adult respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC) are serious complications of sepsis. Thrombomodulin, an important endothelial anticoagulant, binds thrombin to generate activated protein C (APC). To determine whether thrombomodulin purified from human urine (urinary thrombomodulin, UTM) is useful for the treatment of DIC and ARDS in sepsis, we examined the effect of UTM on endotoxin (ET)‐induced coagulation abnormalities and pulmonary vascular injury in rats. Intravenous administration of UTM prevented the ET‐induced pulmonary accumulation of leukocytes and the increase in pulmonary vascular permeability, as well as ET‐induced histological changes such as leukocyte infiltration and pulmonary interstitial edema. On the other hand, dansyl‐Glu‐Gly‐Arg‐chloromethyl ketone‐treated factor Xa (DEGR‐Xa), a selective inhibitor of thrombin generation, did not prevent these effects of ET. UTM did not prevent ET‐induced pulmonary accumulation of leukocytes and pulmonary vascular injury in rats pretreated with DEGR‐Xa. Our findings suggest that UTM attenuates ET‐induced coagulation abnormalities and pulmonary vascular injury. Furthermore, the latter effect may be dependent on the capacity of UTM to activate protein C. Am. J. Hematol. 54:118–123 © 1997 Wiley‐Liss, Inc.