NEUTROPHIL MIGRATION ACROSS A CULTURED INTESTINAL EPITHELIUM - DEPENDENCE ON A CD11B CD18-MEDIATED EVENT AND ENHANCED EFFICIENCY IN PHYSIOLOGICAL DIRECTION
NEUTROPHIL MIGRATION ACROSS A CULTURED INTESTINAL EPITHELIUM - DEPENDENCE ON A CD11B CD18-MEDIATED EVENT AND ENHANCED EFFICIENCY IN PHYSIOLOGICAL DIRECTION
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DOI：
10.1172/jci115473
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发表时间：
1991-11-01
影响因子：
15.9
通讯作者：
MADARA, JL
中科院分区：
文献类型：
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作者：
PARKOS, CA;DELP, C;MADARA, JL
中性粒细胞（PMN）在许多疾病状态下迁移穿过肠上皮。尽管这种迁移是疾病活动的组织学指标，但关于pmn -肠上皮相互作用的分子事件知之甚少。我们研究了趋化肽驱动PMN在培养的人肠上皮细胞系T84单层细胞中的移动。通过微量迁移测定，我们发现转移上皮阻力（76 +/- 3%）和迁移（4 +/- 0.6 × 10(5) PMN）均降低。当PMN施加在6 × 10(6)时，cm-2。单克隆抗体可以识别PMN表面异二聚体粘附糖蛋白CD11b/CD18的亚基，从而在很大程度上阻止cm-2)的发生。相比之下，这种pmn -上皮相互作用不受单克隆抗体识别其余两个α亚基CD11a或CD11c的影响。来自白细胞粘附缺陷患者的PMN也未能跨上皮单层迁移，从而证实了对CD11/18整合素的需求。通过修改我们的微测定，我们能够在生理方向上评估PMN在T84单层上的迁移（由于技术原因，尚未在上皮中进行研究）：单抗对CD18或CD11b的迁移再次大大减弱（分别抑制86 +/- 2%和73 +/- 3%），但单抗对CD11a， CD11c的迁移不受影响。在PMN密度标准条件下，生理方向的PMN迁移效率是常规研究的相反方向的5-20倍。
Neutrophils (PMN) migrate across intestinal epithelia in many disease states. Although such migration serves as a histological index of disease activity, little is known concerning the molecular events underlying PMN-intestinal epithelial interactions. We have studied chemotactic peptide-driven movement of PMN across cultured monolayers of the human intestinal epithelial cell line T84. Using a transmigration microassay, we show that both the decreased transepithelial resistance (76 +/- 3%) and transmigration (4 +/- 0.6 X 10(5) PMN.cm-2, when PMN applied at 6 X 10(6) . cm-2) are largely prevented by MAbs which recognize either subunit of the PMN surface heterodimeric adhesion glycoprotein, CD11b/CD18. In contrast, such PMN-epithelial interactions are unaffected by MAbs recognizing either of the remaining two alpha-subunits CD11a or CD11c. PMN from a leukocyte adherence deficiency patient also failed to migrate across epithelial monolayers thus confirming a requirement for CD11/18 integrins. By modifying our microassay, we were able to assess PMN transmigration across T84 monolayers in the physiological direction (which, for technical reasons, has not been studied in epithelia): transmigration was again largely attenuated by MAb to CD18 or CD11b (86 +/- 2% and 73 +/- 3% inhibition, respectively) but was unaffected by MAb to CD11a, CD11c. For standard conditions of PMN density, PMN transmigration in the physiological direction was 5-20 times more efficient than in the routinely studied opposite direction.