HUMAN LEUKOAGGLUTINATING ANTIBODY EVOKES COOPERATIVE LEUKOTRIENE SYNTHESIS IN PULMONARY MICROVASCULATURE - MODEL OF TRANSFUSION-RELATED ACUTE LUNG INJURY

被引:18
作者
GRIMMINGER, F
KREUSLER, B
SCHNEIDER, U
VONWITZLEBEN, E
WALMRATH, D
NEPPERT, J
SEEGER, W
机构
[1] UNIV GIESSEN,DEPT INTERNAL MED,KLIN STR 36,W-6300 GIESSEN,GERMANY
[2] GERMAN RED CROSS,CTR BLOOD,MANNHEIM,GERMANY
关键词
COOPERATIVE EICOSANOID SYNTHESIS; COMPLEMENT; GRANULOCYTE ANTIBODY; LEUKOTRIENES; TRANSFUSION-RELATED ACUTE LUNG INJURY;
D O I
10.1161/01.RES.68.2.503
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Leukoagglutinating antibodies have been implicated in the development of transfusion-related acute lung injury. In the present study, human neutrophil leukotriene generation was provoked by an anti-5b immunoglobulin G, isolated from a multiparous donor plasma that caused noncardiogenic lung edema during transfusion therapy. In 5b-positive polymorphonuclear neutrophils (PMNs), the antibody stimulated marked arachidonic acid metabolism, dependent on the presence of plasma as the complement source. Quantity and profile of lipid mediators (leukotriene B4 and its omega-oxidation products, 5-hydroxyeicosatetraenoic acid, and nonenzymatic hydrolysis products of leukotriene A4) corresponded to those repeatedly described after PMN in vitro stimulation with the artificial calcium ionophore A23187. Anti-5b challenge of PMNs sequestered in the microvasculature of perfused rabbit lungs did, however, induce a markedly modified metabolite profile. Nonenzymatic hydrolysis products of leukotriene A4 were not detected, and 5-hydroxyeicosatetraenoic acid was markedly reduced. In contrast, cysteinyl leukotrienes were measured as predominant compounds, with rapid appearance of leukotriene C4 and more protracted generation of leukotriene E4. Leukotriene B4 and its omega-oxidation products were released with similar kinetics, but in lower amounts, as compared with the isolated PMN stimulation. Anti-5b challenge of PMNs coincubated with pulmonary artery endothelial cells in vitro, but not stimulation of either cell type alone, provoked marked generation of cysteinyl leukotriene A4 transfer to adjacent acceptor cells with subsequent enzymatic conversion to cysteinyl leukotrienes under conditions of lung vascular sequestration. Endothelial cells appear to serve as predominant cooperative cells under circumstances of blood-free lung perfusion. PMN-related transcellular eicosanoid synthesis may be involved in the pathogenesis of transfusion-evoked acute lung injury.
引用
收藏
页码:503 / 512
页数:10
相关论文
共 46 条
  • [1] ANDREWS AT, 1976, AM J CLIN PATHOL, V66, P483
  • [2] BIGBY TD, 1989, J IMMUNOL, V143, P1948
  • [3] LEUKOAGGLUTINATION WITH INTERSTITIAL PULMONARY-EDEMA - A COMPLICATION OF DONOR-SPECIFIC TRANSFUSION
    CAMPBELL, DA
    SWARTZ, RD
    WASKERWITZ, JA
    HAINES, RF
    TURCOTTE, JG
    [J]. TRANSPLANTATION, 1982, 34 (05) : 300 - 301
  • [4] CARILLI AD, 1978, CHEST, V74, P310, DOI 10.1378/chest.74.3.310
  • [5] HUMAN-ENDOTHELIAL CELLS STIMULATE LEUKOTRIENE SYNTHESIS AND CONVERT GRANULOCYTE RELEASED LEUKOTRIENE-A4 INTO LEUKOTRIENE-B4, LEUKOTRIENE-C4, LEUKOTRIENE-D4 AND LEUKOTRIENE-E4
    CLAESSON, HE
    HAEGGSTROM, J
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1988, 173 (01): : 93 - 100
  • [6] LEUKOTRIENE-C4 PRODUCTION BY MURINE MAST-CELLS - EVIDENCE OF A ROLE FOR EXTRACELLULAR LEUKOTRIENE-A4
    DAHINDEN, CA
    CLANCY, RM
    GROSS, M
    CHILLER, JM
    HUGLI, TE
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (19) : 6632 - 6636
  • [7] MARGINATED POOL OF NEUTROPHILS IN RABBIT LUNGS
    DOERSCHUK, CM
    ALLARD, MF
    MARTIN, BA
    MACKENZIE, A
    AUTOR, AP
    HOGG, JC
    [J]. JOURNAL OF APPLIED PHYSIOLOGY, 1987, 63 (05) : 1806 - 1815
  • [8] DOUKAS J, 1988, BLOOD, V71, P771
  • [9] NOVEL TRANS-CELLULAR INTERACTION - CONVERSION OF GRANULOCYTE-DERIVED LEUKOTRIENE A4 TO CYSTEINYL-CONTAINING LEUKOTRIENES BY HUMAN-PLATELETS
    EDENIUS, C
    HEIDVALL, K
    LINDGREN, JA
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1988, 178 (01): : 81 - 86
  • [10] ENGELFRIET CP, 1984, ADV IMMUNOBIOLOGY BL, P121