title: Immobilization of rolling NK cells on platelet-borne P-selectin under flow by proinflammatory stimuli, interleukin-12, and leukotriene B4.
abstract: Recruitment of leukocytes from bloodstream to extrahematic sites is tightly regulated by a variety of adhesion molecules that are expressed on the leukocytes and the vessel walls. In this manuscript, we describe the interactions between natural killer (NK) cells and activated, autologous platelets under physiologic flow. We found that surface-adherent human platelets are capable of recruiting human NK cells from flow and that this recruitment is characterized by an initial tethering followed by a rolling phase. Both phases were dependent on the adhesion molecule P-selectin and its counter-ligand on the NK cells (P-selectin glycoprotein ligand 1). Activation of rolling NK cells with inflammatory mediators commonly found in atherosclerotic plaques (interleukin-12 and leukotriene B4) causes immediate cessation of the rolling process and conversion to stationary adhesion. Blocking antibodies to the adhesion molecules membrane-activated complex-1 and leukocyte function antigen-1 inhibited this conversion. Our data suggest that platelets deposited at sites of vascular injury may provide an alternative substrate to endothelial cells for initial recruitment of NK cells to the vessel wall. This may result in extravasation of the NK cells if the appropriate chemotactic signal is applied. These data implicate the P-selectin and integrin family of adhesion molecules in the recruitment of NK cells to atherosclerotic sites.
authors.affiliation: Biological and Medical Research Department, MBC 03, King Faisal Specialist Hospital & Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia.
authors.forename: S
authors.initials: S
authors.lastname: Sheikh
authors.forename: R S
authors.initials: RS
authors.lastname: Parhar
authors.forename: R
authors.initials: R
authors.lastname: Bakheet
authors.forename: S
authors.initials: S
authors.lastname: Saleh
authors.forename: K
authors.initials: K
authors.lastname: Collison
authors.forename: F
authors.initials: F
authors.lastname: Al-Mohanna
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D001792:Blood Platelets / Q000276:immunology* / Q000378:metabolism; D018821:CD18 Antigens / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000494:pharmacology*; D018664:Interleukin-12 / Q000276:immunology / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D007975:Leukotriene B4 / Q000276:immunology / Q000494:pharmacology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000276:immunology; D019007:P-Selectin / Q000276:immunology*
chemical_list: D000906:Antibodies; D018821:CD18 Antigens; D018836:Inflammation Mediators; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D019007:P-Selectin; D018664:Interleukin-12; D007975:Leukotriene B4