Abstract

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.

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