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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.

The incidence of asthma is on the increase worldwide, yet the pathogenesis of this disease is still not fully understood. Many recent drug trials have had disappointing results, thus fuelling the need for more research to be undertaken in this area. Substantial evidence suggests an important role for platelets in various inflammatory diseases, including atherosclerosis, rheumatoid arthritis, eczema, allergic rhinitis and asthma. In asthma, platelets have been found to actively participate in most of its main features, including bronchial hyperresponsiveness, bronchoconstriction, airway inflammation and airway remodelling. It has recently become clear that platelet-release products, as well as the expression of adhesion molecules on the platelet surface and the ability to undergo chemotaxis, are all involved in these processes. This review focuses on both experimental and clinical studies available to date that have investigated the role of platelets in the pathophysiology of asthma. Taken together, the evidence points toward platelets being an attractive new target in the area of asthma research; a target with much-needed novel therapeutic potential.