Minami K, Murata K, Lee C-Y, Fox-Talbot K, Wasowska B A, Pescovitz M D, Baldwin W M
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Am J Transplant. 2006 May;6(5 Pt 1):923-32. doi: 10.1111/j.1600-6143.2006.01281.x.
Antibody-mediated rejection of human cardiac transplants is correlated with C4d deposits and macrophage infiltrates in capillaries of endomyocardial biopsies. We produced an antibody to rat C4d to study C4d deposition and clearance in Lewis rats that were sensitized with a blood transfusion from DA rats 7, 14 or 21 days before cardiac transplantation. Cyclosporin A (CsA) immunosuppression was initiated after transplantation at a dose that inhibited graft rejection, antibody production and C4d deposition in unsensitized recipients. Blood transfusion elicited high levels of circulating IgG alloantibodies, predominantly of the complement-activating IgG2b subclass, that peaked 14 days after transplantation. At this time, macrophages accumulated in capillaries, and C4d deposits were diffuse and intense on arteries, capillaries and veins. Grafts that survived 90 days in sensitized recipients still had deposits of C4d that were associated with increased interstitial fibrosis and vasculopathy in arteries. Clearance of C4d was determined by retransplanting DA cardiac allografts from Lewis recipients back to DA recipients. C4d deposits were decreased to minimal levels within 5 days after retransplantation. Thus, C4d deposition is not limited to the capillaries, but extends throughout the arterial tree, and despite formation of a covalent bond, C4d is cleared within days.
人类心脏移植的抗体介导排斥反应与心内膜活检毛细血管中的C4d沉积及巨噬细胞浸润相关。我们制备了一种针对大鼠C4d的抗体，以研究在心脏移植前7、14或21天接受来自DA大鼠输血致敏的Lewis大鼠中C4d的沉积和清除情况。移植后开始使用环孢素A（CsA）进行免疫抑制，剂量为可抑制未致敏受体的移植物排斥、抗体产生和C4d沉积。输血引发了高水平的循环IgG同种抗体，主要是补体激活的IgG2b亚类，在移植后14天达到峰值。此时，巨噬细胞在毛细血管中积聚，动脉、毛细血管和静脉上的C4d沉积弥漫且强烈。在致敏受体中存活90天的移植物仍有C4d沉积，这与动脉间质纤维化和血管病变增加有关。通过将Lewis受体的DA心脏同种异体移植物再次移植回DA受体来确定C4d的清除情况。再次移植后5天内，C4d沉积降至最低水平。因此，C4d沉积不仅限于毛细血管，还延伸至整个动脉树，并且尽管形成了共价键，C4d在数天内仍可清除。
