During activation PMN generate and release eicosanoids such as leukotriene B4 (Fig. 1), a potent chemoattractant involved in the recruitment of additional PMN to the initial site of invasion or encounter with microbes. There are many ways in which a PMN can impart damage to the lung or other organs and a more complete understanding of this process and the regulation of innate immunity may lead to new approaches to prevent neutrophil-mediated tissue injury. Because PMN-derived materials have been implicated as key components in a wide range of diseases—including myocardial infarction, arthritis, inflammatory bowel disease, asthma, glomerulonephritis, skin disorders, second organ-reperfusion injury and adult respiratory distress syndrome (ARDS)—it is essential to identify animal models that are informative as well as predictive to assess molecular events of importance in neutrophil-mediated tissue injury. On page 42, Nagase et al. 1 do just this.

ARDS is also known as adult respiratory failure, diffuse alveolar damage, acute alveolar injury and traumatic wet lung, terms that denote the diffuse alveolar capillary damage that gives rise to pulmonary edema2. Clinically, onset is marked by the rapid development of severe life-threatening respiratory insufficiency. Both direct lung injuries as well as systemic disorders can contribute to the clinical picture (Fig. 1). This syndrome is characterized by edema or leakage of fluids into the interstitial compartment resulting from injury of the vascular endothelium and/or alveolar epithelial cell damage that can in turn lead to microvascular injury (Fig. 1). Inappropriate PMN activation and spillage of their noxious armament in the proximity of alveolar epithelium and vascular endothelium is thought to be key in the development of ARDS and related disorders that can lead to fibrosis and irreversible damage of the host’s own tissues2. In addition to the PMN, macrophages can also participate and contribute to the injury, releasing their own array of proinflammatory chemical mediators, including chemokines, cytokines, eicosanoids and additional lipid mediators such as platelet-activating factor. Indeed, the activation of platelets and other resident cell types of the lung further amplifies the recruitment of phagocytic cells. Because the edema and the inflammatory infiltrate are rapid in onset, it is a useful experimental system to study with implications for many other diseases that are chronic in duration. In this context, temporal relationship (s) between inflammatory mediators and appropriateness of animal models to human disease pathogenesis are ongoing subjects of discussion, particularly for complex multifactorial diseases where decades are required to develop symptoms (such as atherosclerosis). Thus, the clinical picture for ARDS, with its diffuse edema resulting from microvascular injury, apparently has the complete cast of mediators, but in “fast forward” compared to other inflammation-associated diseases. Leukotriene B4, among the most potent endogenous chemoattractants (along with