ADHESION MOLECULE EXPRESSION DURING NEUTROPHIL CHEMOTAXIS

中性粒细胞趋化过程中粘附分子的表达

• 批准号: 3770440
• 负责人: L HARVATH
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3770440
• 关键词: CD antigens; basement membrane; cell migration; chemoattractants; chemotaxis; flow cytometry; gene expression; gene induction /repression; human tissue; leukocyte adhesion molecules; neutrophil; peptides; vascular endothelium

Neutrophil mobilization to inflammatory sites is a multi-step process which involves the reversible adhesion to specific endothelial plasma membrane molecules, upregulation of selected neutrophil adhesion molecules during chemoattractant exposure, and migration (chemotaxis) through endothelial gaps and the basement membrane into tissues. The present study was undertaken to examine the changes that occur in adhesion molecule expression during neutrophil chemotaxis in vitro. Two populations of neutrophils are easily identified and separated with the in vitro polycarbonate membrane system; one population does not migrate to chemoattractant (nonmigrating population) and remains on the upper surface of the membrane, whereas the other population migrates through the membrane pores to the lower surface of the membrane (migrating population). Neutrophils, incubated in suspension with or without the N-formyl peptide (FMLP), were compared with the migrating and nonmigrating subpopulations which were exposed to a gradient of FMLP. Neutrophils were stained with a panel of adhesion molecule monoclonal antibodies which recognize: the leukocyte-cell adhesion molecule family (Leu-CAM), CD11a, CD11b, and CD11c; the platelet/ endothelial cell adhesion molecule-1 (PECAM-1), CD31; leukosialin, CD43; and, the homing receptor Pgp-1, CD44. Flow cytometric analysis of the panel revealed that the migrating subpopulation consistently exhibited less surface expression of these adhesion molecules than the nonmigrating subpopulation. CD44, CD43, and CD11a were the most dramatically decreased (49-60%), whereas, CD11c, CD31, and CD11b were moderately decreased (25-38%). Expression of a control antigen, CD15, remained unchanged in migrating and nonmigrating neutrophils. These results indicate that neutrophil adhesion molecule expression is differentially downregulated during neutrophil chemotaxis. This experimental system provides a means for quantifying the expression of myeloid antigens which are important in inflammatory responses.

炎症部位的神经元动员是一个多步骤的过程， 涉及对特异性内皮细胞质膜的可逆粘附 分子，选择的中性粒细胞粘附分子在 化学引诱物暴露和通过内皮细胞的迁移（趋化性） 间隙和基底膜进入组织。 本研究 研究粘附分子发生的变化， 在体外中性粒细胞趋化过程中表达。 两个种群 中性粒细胞很容易识别和分离与体外 聚碳酸酯膜系统;一个种群不会迁移到 化学引诱物（非迁移种群），并保留在上表面 而另一个种群则通过膜迁移 孔到膜的下表面（迁移群体）。 中性粒细胞，在含或不含N-甲酰肽的悬浮液中孵育 （FMLP），与迁移和非迁移亚群进行了比较 它们被暴露在FMLP的梯度下。 中性粒细胞用 一组粘附分子单克隆抗体，其识别： 白细胞-细胞粘附分子家族（Leu-CAM）、CD 11 a、CD 11b和CD 11 c; 血小板/内皮细胞粘附分子-1（PECAM-1），CD 31; 白唾液酸，CD 43;和归巢受体Pgp-1，CD 44。 流式细胞术 专家组的分析显示， 这些粘附分子的表面表达始终较少 比非迁徙的亚群要多。 CD 44、CD 43和CD 11 a在胃癌中的表达最高 显著降低（49-60%），而CD 11 c、CD 31和CD 11b 中度下降（25-38%）。 对照抗原CD 15的表达， 在迁移和非迁移中性粒细胞中保持不变。 这些 结果表明，中性粒细胞粘附分子的表达， 在中性粒细胞趋化过程中差异下调。 这 实验系统提供了一种用于定量表达 在炎症反应中重要的髓样抗原。