FRACTALKINE AND CX(3)CR1 MEDIATE A NOVEL MECHANISM OF LEUKOCYTE CAPTURE, FIRM ADHESION, AND ACTIVATION UNDER PHYSIOLOGICAL FLOW

Leukocyte migration into sites of inflammation involves multiple molec ular interactions between leukocytes and vascular endothelial cells, m ediating sequential leukocyte capture, rolling, and firm adhesion. In this study, we tested the role of molecular interactions between fract alkine (FKN), a transmembrane mucin-chemokine hybrid molecule expresse d on activated endothelium, and its receptor (CX(3)CR1) in leukocyte c apture, firm adhesion, and activation under physiologic flow condition s. Immobilized FKN fusion proteins captured resting peripheral blood m ononuclear cells at physiologic wall shear stresses and induced firm a dhesion of resting monocytes, resting and interleukin (IL)-2-activated CD8(+) T lymphocytes and IL-2-activated NK cells. FKN also induced ce ll shape change in firmly adherent monocytes and IL-2-activated lympho cytes. CX(3)CR1-transfected K562 cells, but not control K562 cells, fi rmly adhered to FKN-expressing ECV-304 cells (ECV-FKN) and tumor necro sis factor alpha-activated human umbilical vein endothelial cells. Thi s firm adhesion was not inhibited by pertussis toxin, EDTA/EGTA, or an tiintegrin antibodies, indicating that the firm adhesion was integrin independent. In summary, FKN mediated the rapid capture, integrin-inde pendent firm adhesion, and activation of circulating leukocytes under now. Thus, FKN and CX(3)CR1 mediate a novel pathway for leukocyte traf ficking.