title: Circulating platelet-neutrophil complexes are important for subsequent neutrophil activation and migration.
abstract: Previous studies in our laboratory have shown that platelets are essential for the migration of eosinophils into the lungs of allergic mice, and that this is dependent on the functional expression of platelet P-selectin. We sought to investigate whether the same is true for nonallergic, acute inflammatory stimuli administered to distinct anatomic compartments. Neutrophil trafficking was induced in two models, namely zymosan-induced peritonitis and LPS-induced lung inflammation, and the platelet dependence of these responses investigated utilizing mice rendered thrombocytopenic. The relative contribution of selectins was also investigated. The results presented herein clearly show that platelet depletion (>90%) significantly inhibits neutrophil recruitment in both models. In addition, we show that P-selectin glycoprotein ligand-1, but not P-selectin, is essential for neutrophil recruitment in mice in vivo, thus suggesting the existence of different regulatory mechanisms for the recruitment of leukocyte subsets in response to allergic and nonallergic stimuli. Further studies in human blood demonstrate that low-dose prothrombotic and pro-inflammatory stimuli (CCL17 or CCL22) synergize to induce platelet and neutrophil activation, as well as the formation of platelet-neutrophil conjugates. We conclude that adhesion between platelets and neutrophils in vivo is an important event in acute inflammatory responses. Targeting this interaction may be a successful strategy for inflammatory conditions where current therapy fails to provide adequate treatment.
authors.affiliation: Sackler Institute of Pulmonary Pharmacology and Therapeutics, Division of Pharmaceutical Sciences, School of Biomedical and Health Sciences, King’s College, London, UK. k.n.kornerup@qmul.ac.uk
authors.forename: Kristin N
authors.initials: KN
authors.lastname: Kornerup
authors.forename: Gary P
authors.initials: GP
authors.lastname: Salmon
authors.forename: Simon C
authors.initials: SC
authors.lastname: Pitchford
authors.forename: Wai L
authors.initials: WL
authors.lastname: Liu
authors.forename: Clive P
authors.initials: CP
authors.lastname: Page
mesh_terms: D000328:Adult; D000818:Animals; D001792:Blood Platelets / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002066:Busulfan; D018821:CD18 Antigens / Q000097:blood; D002478:Cells, Cultured; D054414:Chemokine CCL17 / Q000378:metabolism; D054422:Chemokine CCL22 / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D018375:Neutrophil Activation; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology*; D019007:P-Selectin / Q000097:blood; D010538:Peritonitis / Q000097:blood / Q000139:chemically induced / Q000276:immunology*; D010973:Platelet Adhesiveness; D011014:Pneumonia / Q000097:blood / Q000139:chemically induced / Q000276:immunology*; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced / Q000276:immunology; D055815:Young Adult; D015054:Zymosan
chemical_list: D018821:CD18 Antigens; C499538:Ccl17 protein, mouse; C515483:Ccl22 protein, mouse; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D015054:Zymosan; D002066:Busulfan