2006 - UZ Leuven

GEUDENS N., VAN DE WOUWER M., VANAUDENAERDE B.M.,NEYRINCK A.P., REGA F.R., VAN DE WAUXER C., LERUT T.,VERBEKEN E., VERLEDEN G.M., CONWAY Ed., VAN RAEMDONCKD.E.M.: The lecitin-like domain of thrombomodulin supressesleukocytose lung infiltration in a murine ischemia-reperfusion injurymodel. Eur. Resp. Journal, 2006; 28(50): p. 779s.Background: Thrombomodulin (TM) is a vascular endothelial cellreceptor that is a cofactor for thrombin-mediated activation of the anticoagulantand anti-inflammatory properties. In this study weinvestigated the role of this domain on lung ischemia-reperfusioninjury, which remains an important risk factor for the early survival oflung transplant recipients. The use of wild-type (TM wt/wt ) andtransgenic (TM LeD/LeD ) mice, the latter which lack the N-terminal lectinlikedomain of TM, could give us a better insight on proteins importantin leukocyte infiltration in the lung.Methods: In female TM LeD/LeD and TM wt/wt mice (n=6/group), the hilumof the left lung was clamped to induce warm in situ ischemia for 90minutes, followed by 4 hours of reperfusion. After sacrifice, BAL wasobtained by instillation of saline in the left lung for cell count.Results: (mean±SD) are listed in TableBALCells(x10 4 /ml)Macrophages(x10 4 /ml)Lymphocytes(x10 4 /ml)Neutrophils(x10 4 /ml)TM wt/wt mice 96.0 ± 22.0 72.8 ± 17.6 16.9 ± 6.1 6.2 ± 3.4TM LeD/LeD 139.3 ± 16.5** 101.8 ± 19.9* 17.2 ± 4.7 20.4 ± 5.0******: p < 0.001; **: p < 0.01 and * p < 0.05 versus TM wt/wt miceConclusion: The lack of the N-terminal lectin-like domain of TMdampens the inflammatory cellular respons after ischemia andreperfusions in the mouse lung. This domain could be an interestingtarget to modulate the inflammatory status following lungtransplantation.JACQUEMIN M., NEYRINCK A., HERMANNS M.I., LAVEND’HOMME R.,REGA F., SAINT-REMY J.M., PEERLINCK K., VAN RAEMDONCK D.,KIRKPATRICK C.J.: FVIII production by human lung microvascularendothelial cells. Blood, 2006; 108(2): 515-517.While extrahepatic factor VIII (FVIII) synthesis suffices for hemostasis,the extrahepatic production sites are not well defined. We thereforeinvestigated the ability of the human lungs to produce FVIII. Lungsfrom heart-beating donors who were declined for transplantation wereperfused and ventilated in an isolated reperfusion model for 2 hours. A102