Apoptosis in murine cardiac grafts.
Apoptosis in murine cardiac grafts.
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小鼠心脏移植物中的细胞凋亡。
DOI：
10.1097/00007890-199701270-00025
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发表时间：
1997
期刊：
影响因子：
6.2
通讯作者：
Orosz,CG
中科院分区：
文献类型：
--
作者：
Bergese,SD;Klenotic,SM;Wakely,ME;Sedmak,DD;Orosz,CG
细胞凋亡或诱导程序性细胞死亡是细胞毒性T细胞通常用于引起靶细胞裂解的机制。我们评估了DBA/2→ DBA/2异位心脏同种移植物、急性排斥DBA/2→ C57 BL/6心脏同种移植物和接受60天DBA/2→ C57 BL/6同种移植物中凋亡细胞的频率和分布。5)或硝酸镓（GN）。通过TUNEL法分析细胞核DNA片段，在组织切片中鉴定细胞凋亡。我们观察到以下情况。(1)心脏同种移植物未显示可检测的TUNEL+细胞。(2)排斥性心脏同种异体移植物显示罕见的（< 1%的有核细胞/视野）、弥漫性TUNEL+细胞，在第3天达到峰值，并在排斥当天（约第10天）下降至峰值的50%，并且TUNEL+细胞定位于细胞浸润区域而不是肌细胞区域。(3)接受的心脏同种异体移植物显示出相对高数量的TUNEL+细胞，定位于大心脏动脉内和周围（约20%的有核细胞/动脉周围区域）。这些动脉经常表现出移植血管硬化的证据，这是慢性同种异体移植排斥反应的特征。虽然在动脉组织中发现了少数TUNEL+细胞，但在动脉周围细胞浸润中观察到了大多数。在接受抗CD 4 mAb GK 1.5或硝酸镓治疗的移植物中观察到相似的TUNEL+细胞频率和分布。总的来说，细胞凋亡与移植失败或实质细胞损伤无关，表明细胞毒性T细胞介导的移植组织破坏在心脏同种异体移植物中是罕见的。虽然细胞凋亡似乎并不表示急性排斥反应，但接受的移植物中细胞凋亡的特征性动脉周围聚集可能表示维持移植物接受的免疫调节过程或促进慢性血管重塑的修复过程。
Apoptosis, or the induction of programmed cell death, is a mechanism commonly used by cytotoxic T cells to cause target cell lysis. We evaluated the frequency and distribution of apoptotic cells in DBA/2→ DBA/2 heterotopic cardiac isografts, acutely rejecting DBA/2→ C57BL/6 cardiac allografts, and accepted, 60 day DBA/2→ C57BL/6 allografts from mice treated with anti-CD4 Mab (GK1. 5) or gallium nitrate (GN). Apoptosis was identified in histologic sections via TUNEL analysis of nuclear DNA fragmentation. We observed the following.(1) Cardiac isografts display no detectable TUNEL+ cells.(2) Rejecting cardiac allografts display rare (< 1% of nucleated cells/field), diffuse TUNEL+ cells, peaking on day 3 and declining to 50% of peak by the day of rejection (approximately day 10), and TUNEL+ cells were localized to regions of cellular infiltrate rather than myocyte regions.(3) Accepted cardiac allografts display relatively high numbers of TUNEL+ cells localized in and around the large cardiac arteries (about 20% of nucleated cells/periarterial field). These arteries often showed evidence of transplant vascular sclerosis characteristic of chronic allograft rejection. While a few TUNEL+ cells were found in the arterial tissue, most were observed in the periarterial cellular infiltrate. Similar frequencies and distributions of TUNEL+ cells were observed in grafts that were accepted due to treatment with the anti-CD4 mAb GK 1.5 or gallium nitrate. In general, apoptosis did not correlate with graft failure or parenchymal cell damage, suggesting that cytotoxic T cell-mediated destruction of graft tissues is rare in cardiac allografts. While apoptosis does not appear to be indicative of acute rejection, the characteristic periarterial clustering of apoptosis in accepted grafts may be indicative of immunoregulatory processes that maintain graft acceptance or repair processes that promote chronic vascular remodeling.