Published ahead of print on October 31, 2008, doi:10.1165/rcmb.2008-0348TR
© 2009 American Thoracic Society DOI: 10.1165/rcmb.2008-0348TR
Transepithelial Migration of NeutrophilsMechanisms and Implications for Acute Lung Injury1 Division of Pulmonary and Critical Care Medicine, Department of Medicine, National Jewish Health, Denver; 2 Division of Pulmonary Sciences and Critical Care Medicine; 3 Mucosal Inflammation Program; 4 Division of Gastroenterology, Department of Medicine; and 5 Integrated Department of Immunology, University of Colorado Denver, Aurora, Colorado Correspondence and requests for reprints should be addressed to Gregory P. Downey, M.D., Drs Harold and Mary Zirin Chair in Pulmonary Biology, K701b, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206. E-mail: downeyg{at}njhealth.org The primary function of neutrophils in host defense is to contain and eradicate invading microbial pathogens. This is achieved through a series of swift and highly coordinated responses culminating in ingestion (phagocytosis) and killing of invading microbes. While these tasks are usually performed without injury to host tissues, in pathologic circumstances such as sepsis, potent antimicrobial compounds can be released extracellularly, inducing a spectrum of responses in host cells ranging from activation to injury and death. In the lung, such inflammatory damage is believed to contribute to the pathogenesis of diverse lung diseases, including acute lung injury and the acute respiratory distress syndrome, chronic obstructive lung disease, and cystic fibrosis. In these disorders, epithelial cells are targets of leukocyte-derived antimicrobial products, including proteinases and oxidants. Herein, we review the mechanisms involved in the physiologic process of neutrophil transepithelial migration, including the role of specific adhesion molecules on the leukocyte and epithelial cells. We examine the responses of the epithelial cells to the itinerant leukocytes and their cytotoxic products and the consequences of this for lung injury and repair. This paradigm has important clinical implications because of the potential for selective blockade of these pathways to prevent or attenuate lung injury.
Key Words: inflammation • acute lung injury • tight junctions • adherens junctions • proteolytic enzymes
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