TY - JOUR T1 - Neutrophils Disturb Pulmonary Microcirculation in Sepsis-induced Acute Lung Injury JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.00786-2018 SP - 1800786 AU - Inwon Park AU - Mingyo Kim AU - Kibaek Choe AU - Eunjoo Song AU - Howon Seo AU - Yoonha Hwang AU - Jinhyo Ahn AU - Seung-Hyo Lee AU - Jae Hyuk Lee AU - You Hwan Jo AU - Kyuseok Kim AU - Gou Young Koh AU - Pilhan Kim Y1 - 2019/01/01 UR - http://erj.ersjournals.com/content/early/2019/01/02/13993003.00786-2018.abstract N2 - The lung is highly vulnerable during sepsis, yet its functional deterioration accompanied by disturbances in the pulmonary microcirculation are poorly understood. This study aimed to investigate how the pulmonary microcirculation is distorted in sepsis-induced acute lung injury (ALI) and reveal the underlying cellular pathophysiologic mechanism.Using a customized intravital lung microscopic imaging system in a murine model of sepsis-induced ALI, we achieved direct real-time visualization of the pulmonary microcirculation and circulating cells in vivo. We derived the functional capillary ratio (FCR) as a quantitative parameter for assessing the fraction of functional microvasculature in the pulmonary microcirculation and dead space.We identified that the FCR rapidly decreases in the early stage of sepsis-induced ALI. The intravital imaging revealed that it was the result of the generation of dead space which was induced by prolonged neutrophil entrapment within the capillaries. We further showed that the neutrophils had an extended sequestration time and an arrest-like dynamic behavior, both of which triggered neutrophil aggregates inside the capillaries and arterioles. Finally, we found that Mac-1 (CD11b/CD18) was upregulated in the sequestered neutrophils and that a Mac-1 inhibitor restored the FCR and improved the hypoxemia.With the intravital lung imaging system, we observed how Mac-1 upregulated neutrophil aggregates led to the generation of dead space in the pulmonary microcirculation and its improvement by a Mac-1 inhibitor in sepsis-induced ALI.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Park has nothing to disclose.Conflict of interest: Dr. Kim has nothing to disclose.Conflict of interest: Dr. Choe has nothing to disclose.Conflict of interest: Dr. Song has nothing to disclose.Conflict of interest: Dr. Seo has nothing to disclose.Conflict of interest: Dr. Hwang has nothing to disclose.Conflict of interest: Dr. Ahn has nothing to disclose.Conflict of interest: Dr. S.-H. Lee has nothing to disclose.Conflict of interest: Dr. J. H. Lee has nothing to disclose.Conflict of interest: Dr. Jo has nothing to disclose.Conflict of interest: Dr. Kim has nothing to disclose.Conflict of interest: Dr. Koh has nothing to disclose.Conflict of interest: Dr. Kim has nothing to disclose. ER -