• Muhammad Asaduzzaman, Shahram Lavasani, Milladur Rahman, Su Zhang, Oscar O Braun, Bengt Jeppsson, and Henrik Thorlacius.
• Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden.
• Crit. Care Med. 2009 Apr 1;37(4):1389-96.

ObjectiveRecent findings indicate that platelets not only regulate thrombosis and hemostasis but may also be involved in proinflammatory activities. Herein, we hypothesized that platelets may play a role in sepsis by activating and priming circulating neutrophils for subsequent recruitment into the lung.DesignProspective experimental study.SettingUniversity Hospital Research Unit.SubjectMale C57BL/6 mice.InterventionsLung edema, bronchoalveolar infiltration of neutrophils, levels of myeloperoxidase, expression and function of membrane-activated complex-1 (Mac-1) on neutrophils and the CXC chemokines, macrophage inflammatory protein-2, and cytokine-induced neutrophil chemoattractant were determined after cecal ligation and puncture (CLP). Mice received a platelet-depleting antibody as well as antibodies directed against P-selectin glycoprotein-ligand-1 and Mac-1 before CLP induction.Measurements And Main ResultsCLP caused significant pulmonary damage characterized by neutrophil infiltration, increased levels of CXC chemokines, and edema formation in the lung. Furthermore, CLP up-regulated Mac-1 expression on neutrophils and increased the number of neutrophils binding platelets in the circulation. Interestingly, depletion of platelets reduced CLP-induced edema and neutrophil recruitment in the bronchoalveolar space by >60%. Furthermore, depletion of platelets reduced Mac-1 expression on neutrophils. On the other hand, inhibition of P-selectin glycoprotein-ligand-1 abolished CLP-induced neutrophil-platelet aggregation but had no effect on neutrophil expression of Mac-1.ConclusionsThese data demonstrate that platelets play a key role in regulating infiltration of neutrophils and edema formation in the lung via upregulation of Mac-1 in abdominal sepsis.

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