Loss of endothelial surface expression of E-selectin in a patient with recurrent infections
Loss of endothelial surface expression of E-selectin in a patient with recurrent infections
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DOI：
10.1182/blood.v94.3.884.415a14_884_894
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发表时间：
1999-08-01
期刊：
影响因子：
20.3
通讯作者：
Sullivan, KE
中科院分区：
文献类型：
--
作者：
DeLisser, HM;Christofidou-Solomidou, M;Sullivan, KE
中性粒细胞在炎症部位的聚集是由一组特定的细胞黏附分子介导的，包括白细胞上的β2整合素和选择素(内皮上的P和E选择素，以及白细胞上的L选择素)，这一点得到了白细胞黏附缺陷综合征患者的研究的支持，这些患者的白细胞缺乏β2整合素或选择素碳水化合物配体的表达(例如sialyl-Lewis(X))。然而。参与白细胞募集的内皮细胞黏附分子的遗传性缺陷或功能障碍以前从未被描述过。在这篇报告中，我们描述了一位反复感染的儿童，临床证据显示脓液形成受损，令人联想到白细胞黏附缺陷综合征，但其中性粒细胞功能正常，CD18、L-选择素和唾液酸化刘易斯(X)表达正常。相反，患者炎症组织的免疫组织化学染色显示内皮细胞中没有E-选择素，尽管存在E-选择素mRNA。然而，E-选择素蛋白的表达是因为循环中的可溶性E-选择素水平显著升高，其分子大小与E-选择素的蛋白水解性切割形式一致。基因测序没有显示出隐藏的突变变体的证据。据我们所知，这些数据首次描述了与白细胞募集有关的内皮细胞黏附分子的潜在遗传性功能障碍，并为内皮选择素在炎症反应中的重要性提供了更多的人类证据。(C)1999年由美国血液病学会主办。
Neutrophil accumulation at sites of inflammation is mediated by specific groups of cell adhesion molecules including the beta 2 (CD18) integrins on leukocytes and the selectins (P- and E-selectin on the endothelium and L-selectin on the leukocyte), This is supported by studies of patients with leukocyte adhesion deficiency syndromes whose leukocytes are genetically deficient in the expression of beta 2 integrins or selectin carbohydrate ligands (eg, sialyl-Lewis(x)). However. inherited deficiency or dysfunction of endothelial cell adhesion molecules involved in leukocyte recruitment has not been previously described. In this report we describe a child with recurrent infections and clinical evidence of impaired pus formation reminiscent of a leukocyte adhesion deficiency syndrome, but whose neutrophils were functionally normal and expressed normal levels of CD18, L-selectin, and sialyl Lewis(x). In contrast, immunohistochemical staining of inflamed tissue from the patient showed the absence of E-selectin from the endothelium, although E-selectin mRNA was present. However, E selectin protein was expressed as significantly elevated levels of circulating soluble E selectin were detected, the molecular size of which was consistent with a proteolytically cleaved form of E-selectin. Gene sequencing failed to show evidence of a secreted mutant variant. These data represent, to our knowledge, the first description of a potentially inherited dysfunction of an endothelial cell adhesion molecule involved in leukocyte recruitment and provide additional human evidence of the importance of endothelial selectins in the inflammatory response. (C) 1999 by The American Society of Hematology.