Lomakina Elena B, Waugh Richard E
Department of Pharmacology and Physiology, University of Rochester, Medical Center, Rochester, 601 Elmwood Avenue, Box 711, NY 14642, USA.
Ann Biomed Eng. 2006 Oct;34(10):1553-63. doi: 10.1007/s10439-006-9172-y. Epub 2006 Sep 20.
Changing affinity of beta(2)-integrins on neutrophils for their ligands on endothelium is a critical, regulated step in the inflammatory response. In this report, the dynamics of the neutrophil response to the inflammatory chemokine interleukin-8 (IL-8) is examined. Human IL-8 was immobilized on beads and brought into contact with neutrophils selected from whole blood samples. Resulting changes in cellular adhesion were assessed by measuring the adhesion frequency between a human neutrophil and a bead coated with the endothelial ligand ICAM-1 (intercellular adhesion molecule-1). Cells engulfed the IL-8 coated beads within a few tens of seconds, and most of the cells exhibited an increase in adhesion to ICAM-1 after approximately 5 to 10 min of contact with IL-8 at room temperature (3 to 5 min at 37 degrees C). Neither monocyte chemotactic protein-1 (MCP-1) nor anti-CD45-coated beads caused any changes in adhesion to ICAM-1. IL-8 induced adhesion was blocked by antibody against CD18. At lower surface density of chemokine, approximately 20% of IL-8 coated beads adhered but were not engulfed by the cells, although the increase in adhesion for ICAM-1 was still effected. Heterogeneity in the cellular response and variability between donors was also noted.
改变中性粒细胞上β(2)-整合素对其在内皮细胞上配体的亲和力是炎症反应中一个关键的、受调控的步骤。在本报告中，研究了中性粒细胞对炎症趋化因子白细胞介素-8（IL-8）反应的动力学。将人IL-8固定在珠子上，并使其与从全血样本中选出的中性粒细胞接触。通过测量人中性粒细胞与包被有内皮配体细胞间黏附分子-1（ICAM-1）的珠子之间的黏附频率，评估由此产生的细胞黏附变化。细胞在几十秒内吞噬了包被IL-8的珠子，并且在室温下与IL-8接触约5至10分钟后（37℃时为3至5分钟），大多数细胞对ICAM-1的黏附增加。单核细胞趋化蛋白-1（MCP-1）或抗CD45包被的珠子均未引起对ICAM-1黏附的任何变化。IL-8诱导的黏附被抗CD18抗体阻断。在趋化因子较低表面密度下，约20%包被IL-8的珠子黏附但未被细胞吞噬，尽管对ICAM-1的黏附增加仍然有效。还注意到细胞反应的异质性以及供体之间的变异性。
