Complete reversal of acid-induced acute lung injury by blocking of platelet-neutrophil aggregation
Top Cited Papers
Open Access
- 1 December 2006
- journal article
- Published by American Society for Clinical Investigation in Journal of Clinical Investigation
- Vol. 116 (12) , 3211-3219
- https://doi.org/10.1172/jci29499
Abstract
Acute lung injury (ALI) causes high mortality, but its molecular mechanisms are poorly understood. Acid aspiration is a frequent cause of ALI, leading to neutrophil sequestration, increased permeability, and deterioration of gas exchange. We investigated the role of platelet-neutrophil interactions in a murine model of acid-induced ALI. Acid aspiration induced P-selectin–dependent platelet-neutrophil interactions in blood and in lung capillaries. Reducing circulating platelets or blocking P-selectin halted the development of ALI. Bone marrow chimeras showed that platelet, not endothelial, P-selectin was responsible for the injury. The interaction of platelets with neutrophils and endothelia was associated with TXA2 formation, with detrimental effects on permeability and tissue function. Activated platelets induced endothelial expression of ICAM-1 and increased neutrophil adhesion. Inhibition of platelet-neutrophil aggregation improved gas exchange, reduced neutrophil recruitment and permeability, and prolonged survival. The key findings were confirmed in a sepsis-induced model of ALI. These findings may translate into improved clinical treatments for ALI.Keywords
This publication has 60 references indexed in Scilit:
- Sequential recruitment of neutrophils into lung and bronchoalveolar lavage fluid in LPS-induced acute lung injuryAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2005
- Platelet P-selectin is required for pulmonary eosinophil and lymphocyte recruitment in a murine model of allergic inflammationBlood, 2005
- Thromboxane synthesis is increased by upregulation of cytosolic phospholipase A2 and cyclooxygenase-2 in peripheral polymorphonuclear leukocytes during bacterial infection in childhoodAmerican Journal of Hematology, 2003
- Introduction: The complexities of leukocyte recruitmentSeminars in Immunology, 2002
- A new mathematical model for relative quantification in real-time RT-PCRNucleic Acids Research, 2001
- Mechanisms of Leukocyte Sequestration in Inflamed LungsMicrocirculation, 2001
- The Acute Respiratory Distress SyndromeNew England Journal of Medicine, 2000
- Adhesion of Activated Platelets to Endothelial Cells: Evidence for a GPIIbIIIa-dependent Bridging Mechanism and Novel Roles for Endothelial Intercellular Adhesion Molecule 1 (ICAM-1), αvβ3 Integrin, and GPIbαThe Journal of Experimental Medicine, 1998
- Monocyte tethering by P-selectin regulates monocyte chemotactic protein-1 and tumor necrosis factor-alpha secretion. Signal integration and NF-kappa B translocation.Journal of Clinical Investigation, 1995
- Surfactant Treatment of Respiratory Failure Induced by Hydrochloric Acid Aspiration in RatsAnesthesiology, 1993