Leukocyte integrin Mac-1 promotes acute cardiac allograft rejection

Article

关键词: INTERCELLULAR-ADHESION MOLECULE-1;    ALPHA-INDUCED INFLAMMATION;    GLYCOPROTEIN IB-ALPHA;    CELL-ADHESION;    TRANSENDOTHELIAL MIGRATION;    COUNTER-RECEPTOR;    CR3 CD11B/CD18;    ICAM-1 CD54;    LFA-1;    ACTIVATION;   

DOI  :  10.1161/CIRCULATIONAHA.107.724310

来源: SCIE

【 摘 要 】

Background - In allograft rejection, recipient leukocytes and alloantibodies first target donor endothelial cells. Although the leukocyte integrin Mac-1 (alpha(M beta 2), CD11b/ CD18) facilitates cell - cell interactions among leukocytes and interactions between leukocytes and endothelial cells or platelets, its role in allograft survival and vasculopathy is incompletely defined. Methods and Results - This study examined parenchymal rejection and graft arterial disease after total allomismatched cardiac transplantation ( BALB/ c donor heart and B6 recipients) in wild- type ( WT) and Mac-1- deficient ( Mac-1(-/-)) recipients. Recipient Mac-1 deficiency attenuated parenchymal rejection and significantly prolonged cardiac allograft survival from 8.3 +/- 1.3 days in WT recipient allografts (n= 18) to 13.8 +/- 2.3 days in Mac-1 (-/ -) recipient allografts ( n= 6; P < 0.0001). Accumulation of neutrophils and macrophages significantly decreased in Mac-1 (-/-) compared with WT recipients. Adoptive transfer of WT but not Mac- 1 (-/-) macrophages to Mac- 1 (-/-) recipients exacerbated parenchymal rejection and reduced allograft survival; in contrast, adoptive transfer of WT neutrophils did not affect graft survival. Mac- 1 (-/-) macrophages expressed significantly lower levels of costimulatory molecules both in vivo and in vitro, and mixed lymphocyte reaction using alloantigen- primed Mac-1(-/-) macrophages resulted in significantly lower antigen- presenting function than for WT macrophages. Tumor necrosis factor-alpha production also fell in cultures with Mac- 1(-/-) macrophages. Despite attenuation of acute rejection, recipient Mac- 1- deficiency did not prevent late graft arterial disease. Conclusions - These studies demonstrate critical participation of Mac- 1 in alloresponses during cellular allograft rejection. These observations establish a molecular target for modulating recipient responses to prolong graft survival.

【 授权许可】

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