Myeloid biologyNeutrophil granule contents in the pathogenesis of lung injuryMoraes, Theo Ja; Zurawska, Joanna Hb; Downey, Gregory PbAuthor Information aDivision of Respiratory Medicine, Department of Pediatrics, the Hospital for Sick Children, Toronto, Ontario, Canada bDivision of Respirology, Department of Medicine, The University of Toronto and The Toronto General Hospital Research Institute of University Health Network, Toronto, Ontario, Canada Correspondence to Dr Gregory P. Downey, Clinical Sciences Division, Rm 6264 Medical Sciences Building, University of Toronto, 1 Kings College Circle, Toronto, Ontario, Canada M5S 1A8 Tel: +1 416 978 8923; fax: +1 416 971 2112; e-mail: [email protected] Current Opinion in Hematology: January 2006 - Volume 13 - Issue 1 - p 21-27 doi: 10.1097/01.moh.0000190113.31027.d5 Buy Metrics Abstract Purpose of review This review summarizes recent literature on the role of neutrophil granule contents in acute lung injury and the mechanisms by which these contribute to inflammatory tissue injury. Recent findings Neutrophil products such as elastase, reactive oxygen species, and antimicrobial peptides can alter pulmonary cell function in a nondegradative fashion through activation of cell surface receptors or modulation of signal transduction pathways. These effects can be either beneficial or detrimental to the host. Summary The primary function of neutrophils in the innate immune response – to contain and kill invading microbial pathogens – is achieved through a series of rapid and coordinated responses culminating in phagocytosis and intracellular killing of the pathogens. Neutrophils have a potent antimicrobial arsenal that includes oxidants, proteinases, and cationic peptides. Reactive oxygen species such as oxygen are produced by the phagocyte NADPH oxidase and are microbicidal. Granules within the neutrophil cytoplasm contain potent proteolytic enzymes and cationic proteins that can digest a variety of microbial substrates. These compounds are released directly into the phagosome, compartmentalizing both the pathogen and the cytotoxic products. Under pathological circumstances, however, unregulated release of microbicidal compounds into the extracellular space can paradoxically damage host tissues. Nonspecific inhibition of neutrophils is not clinically realistic, as it would leave the host vulnerable to infection. As the mechanisms of action of neutrophil granule contents are elucidated, therapeutic targets will be identified that will allow for suppression of neutrophils’ detrimental effects while avoiding inhibition of their beneficial effects. © 2006 Lippincott Williams & Wilkins, Inc.