Dong Z M, Murphy J W
Department of Microbiology and Immunology, University of Oklahoma Health Science Center, Oklahoma City 73190, USA.
Infect Immun. 1997 Feb;65(2):557-63. doi: 10.1128/iai.65.2.557-563.1997.
CD18, the beta chain of the beta 2 integrin family of adhesion molecules, is associated with three different alpha chains (CD11a, -b, and -c) and is expressed on the surface of all types of leukocytes. CD18-containing molecules are up-regulated on the surface of neutrophils (polymorphonuclear cells [PMN]) in response to chemotactic agents and are implicated in mediating adhesion to an inflamed endothelium, which is a prerequisite to migration of PMN into infected tissues. In a previous study, we found that a cryptococcal culture filtrate (CneF), when injected into the bloodstream of mice to simulate the antigenemia in cryptococcosis, inhibits PMN accumulation at the site of an inflammatory stimulus. In the present study, we assessed the ability of CneF and its individual components, i.e., glucuronoxylomannan (GXM), galactoxylomannan (GalXM), and mannoprotein (MP), to interact with CD18 on human PMN. CneF labeled with 14C was shown to bind to human PMN in a dose-dependent manner. Pretreatment of PMN with anti-CD18, but not an isotype-matched control monoclonal antibody (MAb) or anti-CD11a MAb, blocked the binding of 14C-labeled CneF to PMN. In addition, CneF, GXM, and GalXM but not MP significantly blocked the binding of the anti-CD18 MAb to CD18 on the surface of unactivated and formyl methionyl leucyl phenylalanine-activated PMN as determined by indirect immunofluorescence staining and flow cytometric analysis. In the same experiments, the cryptococcal polysaccharides did not affect the binding of an anti-CD11a or anti-L-selectin MAb to the surface of PMN at 4 degrees C. The results suggest that CneF and its components GXM and GalXM bind to CD18 on human PMN. Based on our findings, we propose that CD18 is a possible molecular target of cryptococcal polysaccharides and that binding of the polysaccharides to CD18 has the potential to inhibit leukocyte infiltration into inflammatory sites.
CD18是黏附分子β2整合素家族的β链，与三种不同的α链（CD11a、-b和-c）相关联，并在所有类型白细胞的表面表达。含CD18的分子在趋化剂作用下在中性粒细胞（多形核细胞[PMN]）表面上调，并参与介导与炎症内皮的黏附，这是PMN迁移到感染组织的先决条件。在先前的一项研究中，我们发现，当将隐球菌培养滤液（CneF）注入小鼠血液中以模拟隐球菌病中的抗原血症时，它会抑制炎症刺激部位的PMN聚集。在本研究中，我们评估了CneF及其各个组分，即葡糖醛酸木糖甘露聚糖（GXM）、半乳糖木糖甘露聚糖（GalXM）和甘露糖蛋白（MP）与人PMN上的CD18相互作用的能力。结果显示，用14C标记的CneF以剂量依赖的方式与人PMN结合。用抗CD18预处理PMN，但用同型匹配的对照单克隆抗体（MAb）或抗CD11a MAb预处理则不能，可阻断14C标记的CneF与PMN的结合。此外，通过间接免疫荧光染色和流式细胞术分析确定，CneF、GXM和GalXM而非MP可显著阻断抗CD18 MAb与未活化的和甲酰甲硫氨酰亮氨酰苯丙氨酸活化的PMN表面的CD18的结合。在相同实验中，隐球菌多糖在4℃时不影响抗CD11a或抗L-选择素MAb与PMN表面的结合。结果表明，CneF及其组分GXM和GalXM与人PMN上的CD18结合。基于我们的发现，我们提出CD18是隐球菌多糖可能的分子靶点，并且多糖与CD18的结合有可能抑制白细胞浸润到炎症部位。
