Phillips M L, Schwartz B R, Etzioni A, Bayer R, Ochs H D, Paulson J C, Harlan J M
Cytel Corporation, San Diego, California 92121, USA.
J Clin Invest. 1995 Dec;96(6):2898-906. doi: 10.1172/JCI118361.
We have previously reported a newly discovered congenital disorder of neutrophil adhesion, leukocyte adhesion deficiency syndrome type 2 (LAD II). The clinical manifestations of this syndrome are similar to those seen in the classic leukocyte adhesion deficiency syndrome, now designated type 1 (LAD I), but the two syndromes differ in the molecular basis of their adhesion defects. LAD I is caused by a deficiency in the CD18 integrin adhesion molecules while LAD II patients are deficient in expression of sialyl-Lewis X (SLeX), a carbohydrate ligand for selectins. In this report we demonstrate that neutrophils from a LAD II patient bind minimally or not at all to recombinant E-selectin, purified platelet P-selectin, or P-selectin expressed on histamine-activated human umbilical vein endothelial cells, but have normal levels of L-selectin and CD11b/CD18 integrin, and adhere to and migrate across endothelium when CD11b/CD18 is activated. We compare LAD I and LAD II patient neutrophil function in vitro, demonstrating that integrin and selectin adhesion molecules have distinct but interdependent roles in neutrophil adhesion during an inflammatory response.
我们之前报道了一种新发现的中性粒细胞黏附先天性疾病，即2型白细胞黏附缺陷综合征（LAD II）。该综合征的临床表现与经典白细胞黏附缺陷综合征（现称为1型LAD，即LAD I）相似，但这两种综合征在黏附缺陷的分子基础上有所不同。LAD I是由CD18整合素黏附分子缺乏引起的，而LAD II患者的唾液酸化路易斯X（SLeX）表达缺陷，SLeX是一种选择素的碳水化合物配体。在本报告中，我们证明LAD II患者的中性粒细胞与重组E选择素、纯化的血小板P选择素或组胺激活的人脐静脉内皮细胞上表达的P选择素的结合极少或根本不结合，但L选择素和CD11b/CD18整合素水平正常，并且当CD11b/CD18被激活时能够黏附并穿过内皮细胞。我们在体外比较了LAD I和LAD II患者中性粒细胞的功能，证明整合素和选择素黏附分子在炎症反应期间中性粒细胞黏附中具有不同但相互依赖的作用。
