Recombinant thrombomodulin prevents endotoxin-induced lung injury in rats by inhibiting leukocyte activation

被引:44
作者
Uchiba, M
Okajima, K
Murakami, K
Johno, M
Okabe, H
Takatsuki, K
机构
[1] KUMAMOTO UNIV, SCH MED, DEPT LAB MED, KUMAMOTO 860, JAPAN
[2] KUMAMOTO UNIV, SCH MED, DEPT MED, KUMAMOTO 860, JAPAN
[3] KUMAMOTO UNIV, SCH MED, DEPT DERMATOL, KUMAMOTO 860, JAPAN
关键词
recombinant human soluble thrombomodulin; leukocytes; activated protein C;
D O I
10.1152/ajplung.1996.271.3.L470
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Acute respiratory distress syndrome (ARDS) is a serious complication of sepsis. Thrombomodulin, an important endothelial anticoagulant, binds thrombin to generate activated protein C (APC). We have previously demonstrated that APC prevents endotoxin (ET)-induced pulmonary vascular injury by inhibiting activated leukocytes. We therefore examined whether recombinant human soluble thrombomodulin (rhs-TM) prevents activated leukocyte-induced pulmonary vascular injury in rats receiving ET. Intravenous administration of rhs-TM prevented ET-induced pulmonary accumulation of leukocytes and increase in pulmonary vascular permeability, as well as ET-induced histological changes, such as leukocyte infiltration and pulmonary interstitial edema. Dansyl-Glu-Gly-Arg-chloromethyl ketone-treated factor Xa (DEGR-Xa), a selective inhibitor of thrombin generation, did not prevent these effects of ET. rhs-TM did not prevent ET-induced pulmonary accumulation of leukocytes and pulmonary vascular injury in rats pretreated with DEGR-Xa. These results suggest that rhs-TM prevents ET-induced pulmonary vascular injury by inhibiting pulmonary accumulation of leukocytes and that this effect may be mediated primarily by APC generation.
引用
收藏
页码:L470 / L475
页数:6
相关论文
共 37 条
  • [1] ANTITHROMBOTIC EFFECTS OF RECOMBINANT HUMAN SOLUBLE THROMBOMODULIN (RHS-TM) ON ARTERIOVENOUS SHUNT THROMBOSIS IN RATS
    AOKI, Y
    TAKEI, R
    MOHRI, M
    GONDA, Y
    GOMI, K
    SUGIHARA, T
    KIYOTA, T
    YAMAMOTO, S
    ISHIDA, T
    MARUYAMA, I
    [J]. AMERICAN JOURNAL OF HEMATOLOGY, 1994, 47 (03) : 162 - 166
  • [2] BACHOFEN M, 1982, CLIN CHEST MED, V3, P35
  • [3] A SIMPLIFIED PROCEDURE FOR PURIFICATION OF HUMAN-PROTHROMBIN, FACTOR-IX AND FACTOR-X
    BAJAJ, SP
    RAPAPORT, SI
    PRODANOS, C
    [J]. PREPARATIVE BIOCHEMISTRY, 1981, 11 (04): : 397 - 412
  • [4] IDENTIFICATION OF AN INDUCIBLE ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE
    BEVILACQUA, MP
    POBER, JS
    MENDRICK, DL
    COTRAN, RS
    GIMBRONE, MA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (24) : 9238 - 9242
  • [5] INTRAVASCULAR COAGULATION ASSOCIATED WITH ADULT RESPIRATORY-DISTRESS SYNDROME
    BONE, RC
    FRANCIS, PB
    PIERCE, AK
    [J]. AMERICAN JOURNAL OF MEDICINE, 1976, 61 (05) : 585 - 589
  • [6] AN EARLY TEST OF SURVIVAL IN PATIENTS WITH THE ADULT RESPIRATORY-DISTRESS SYNDROME - THE PAO2/FLO2 RATIO AND ITS DIFFERENTIAL RESPONSE TO CONVENTIONAL THERAPY
    BONE, RC
    MAUNDER, R
    SLOTMAN, G
    SILVERMAN, H
    HYERS, TM
    KERSTEIN, MD
    URSPRUNG, JJ
    [J]. CHEST, 1989, 96 (04) : 849 - 851
  • [7] ADULT RESPIRATORY-DISTRESS SYNDROME - SEQUENCE AND IMPORTANCE OF DEVELOPMENT OF MULTIPLE ORGAN FAILURE
    BONE, RC
    BALK, R
    SLOTMAN, G
    MAUNDER, R
    SIVVERMAN, H
    MYERS, TM
    KERSTEIN, MD
    SZIDON, P
    HANLEY, M
    JACOBS, E
    CALDWELL, E
    ALTMAN, F
    BAGWELL, S
    COX, P
    LAMBERT, R
    WILLIAMS, W
    CERRA, F
    BERLAUK, J
    GILMOUR, I
    CLOUTIER, C
    DAVIES, E
    STEINBURG, S
    FEIN, A
    GRANT, M
    MONTAVANI, R
    NEIDERMAN, M
    SKLAREK, H
    GASKILL, H
    LEVINE, B
    HUDSON, L
    DETTENMEIER, P
    WEBB, W
    BELZBERG, H
    MENDOZA, J
    BURCHARD, K
    SMITH, J
    BLACKBURN, J
    BURNS, R
    WEIGELT, J
    URSPRUNG, JJ
    MAILE, M
    WILKS, NE
    DRENNE, K
    [J]. CHEST, 1992, 101 (02) : 320 - 326
  • [8] CHANG SW, 1994, J LAB CLIN MED, V123, P65
  • [9] TUMOR NECROSIS FACTOR-INDUCED LUNG INJURY IS NOT MEDIATED BY PLATELET-ACTIVATING FACTOR
    CHANG, SW
    OHARA, N
    KUO, G
    VOELKEL, NF
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1989, 257 (04): : L232 - L239
  • [10] CLAUSS A., 1957, ACTA HAEMATOL, V17, P237