Circulating platelet-neutrophil complexes represent a subpopulation of activated neutrophils primed for adhesion, phagocytosis and intracellular killing

Platelets play a prominent role in linking the processes of inflammation haemostasis and thrombosis. Recent studies have shown that platelets form heterotypic aggregates with leucocytes via platelet CD62P and leucocyte beta 2 integrins. These interactions have been observed in vitro in blood taken from healthy volunteers and in clinical conditions in which thrombosis and inflammation are prominent. This study investigated the properties of platelet-neutrophil complexes (PNCs) in anticoagulated whole blood. At rest, neutrophils in PNCs exhibit a significantly more activated adhesion molecule profile than free neutrophils with increased CD11b expression and activation (increased binding of the CD11b/CD18 'activation reporter' monoclonal antibody 24) and decreased CD62L expression. In addition, neutrophils in PNCs phagocytosed significantly more Neisseria meningitidis and produced more toxic oxygen metabolites than free neutrophils. Stimulation with the platelet agonist adenosine diphosphate (ADP) led to further increases in CD11b expression and activation, loss of CD62L as well as increased phagocytosis and toxic oxygen metabolite production throughout the whole neutrophil population. When these experiments were repeated with the CD62P blocking antibody G1 the effects were inhibited to a variable extent, dependent upon the parameter under investigation. These results indicate that both soluble and contact-dependent factors contribute to platelet-mediated neutrophil activation. Platelet neutrophil complexes represent a large subpopulation of neutrophils with a more activated adhesion molecule profile, and a greater capacity for phagocytosis and toxic oxygen metabolite production. This study provides further support for a role for PNCs in both health and disease.