Leukocyte Integrin Mac-1 Promotes Acute Cardiac Allograft Rejection
Year: 2008
Type: article
Abstract: BACKGROUND: In allograft rejection, recipient leukocytes and alloantibodies first target donor endothelial cells. Although the leukocyte integrin Mac-1 (alpha(Mbeta2), 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.
Source: Circulation
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1535345869, G204514443, CONTROL OF GROWTH OF VASCULAR WALL CELLS, G2893523848, PATHOGENESIS OF TRANSPLANT ASSOCIATED ARTERIOSCLEROSIS, G3717825497, The IL-18/Caspase-1 cascade in atherosclerosis, G5178112067, Inflammation and Aortic Aneurysm Pathophysiology, Inflammation in Vascular Injury and Repair, Inflammation in Vascular Injury and Repair, Inflammatory Mechanisms of Atherosclerosis, Leptin deficiency changes mast cell pro-inflammatory activity, G773182005, G8184637163, G823643952, G964144134
OpenAlex ID: W2022992883