Importance of CD49d-VCAM interactions in human monocyte adhesion to porcine endothelium.
Importance of CD49d-VCAM interactions in human monocyte adhesion to porcine endothelium.
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CD49d-VCAM 相互作用在人单核细胞与猪内皮细胞粘附中的重要性。
DOI：
10.1111/j.1399-3089.1998.tb00011.x
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Itescu,S
中科院分区：
文献类型：
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作者：
Kwiatkowski,P;Artrip,JH;Ankersmit,J;Schuster,M;John,R;Wang,SF;Ma,N;Michler,RE;Itescu,S
通过使用天然抗体耗竭的灵长类动物模型，我们先前已经表明，在未修饰的灵长类动物受体中，猪心脏异种移植物的延迟排斥是由单核细胞/巨噬细胞谱系细胞的异种移植物浸润引起的。在本研究中，我们最初表明，人单核细胞/巨噬细胞表现出显着更大的粘附未刺激的猪主动脉内皮细胞（PAEC）比人脐静脉内皮细胞（HUVEC）。人TNF-α增加单核细胞与HUVEC的粘附，其水平是PAEC的5倍。这种效应不能根据人TNF-α及其受体在PAEC上的不相容性来解释，因为用TNF-α刺激后，猪VCAM表达增加了75-85%。用抗VCAM单抗处理PAEC或用抗CD 49 d单抗处理单核细胞可消除TNF增强的单核细胞粘附。这些结果表明，VCAM‐ CD 49 d相互作用在人单核细胞与PAEC的粘附中很重要，但可能不如人单核细胞与同种异体内皮细胞之间的相互作用有效，这可能是由于不同物种之间的结构差异。其他尚未确定的相互作用必须解释未刺激的PAEC与HUVEC的人单核细胞的相对增加。在研究这种增强的单核细胞粘附的功能后果的实验中，与HUVEC相比，PAEC刺激诱导的巨噬细胞源性IL-1 β水平高10倍，T细胞增殖水平高3倍。使用抗DR Mab中断自体巨噬细胞的抗原呈递显著降低了T细胞对PAEC的增殖反应。总之，这些结果表明，人单核细胞对PAEC的粘附增强通过导致组织浸润、细胞因子的产生和T细胞异种抗原识别的增强的间接途径而有助于异种移植物排斥超过超急性期。
By using a primate model of natural antibody depletion, we have previously shown that delayed rejection of porcine cardiac xenografts in unmodified primate recipients resulted from xenograft infiltration with monocyte/macrophage lineage cells. In the present study, we initially showed that human monocytes/macrophages demonstrated significantly greater adherence to unstimulated pig aortic endothelial cells (PAEC) than to human umbilical vein endothelial cells (HUVEC). Human TNF‐alpha augmented monocyte adhesion to HUVEC by 5‐fold higher levels than to PAEC. This effect could not be explained on the basis of incompatibility between human TNF‐alpha and its receptor on PAEC since porcine VCAM expression increased by 75–85% after stimulation with TNF‐alpha. TNF‐augmented monocyte adherence was abrogated by either treatment of PAEC with an anti‐VCAM Mab or monocytes with an anti‐CD49d Mab. These results suggest that VCAM‐CD49d interactions are important in adhesion of human monocytes to PAEC but may not be as effective as those between human monocytes and allogeneic endothelium, perhaps because of structural differences across species. Other interactions, as yet undefined, must explain the relative increase in adhesiveness of human monocytes for unstimulated PAEC versus HUVEC. In experiments investigating the functional consequences of this enhanced monocyte adherence, PAEC stimulation induced 10‐fold higher levels of macrophage‐derived IL‐1 beta and 3‐fold higher levels of T cell proliferation compared with HUVEC. Using an anti‐DR Mab to interrupt antigen presentation by autologous macrophages markedly reduced the T cell proliferative response to PAEC. Together, these results indicate that the enhanced adherence of human monocytes to PAEC contributes to xenograft rejection beyond the hyperacute period by leading to tissue infiltration, elaboration of cytokines, and an augmented indirect pathway of T cell xenoantigen recognition.