Among leukocytes, PMNs are considered the first line of defense against microorganisms. Rapidly recruited to the inflammatory site/organ, they exert a variety of primarily beneficial functions (phagocytosis, production of reactive oxygen species [ROS] , and nitric oxide species [NOS] , degranulation of lytic enzymes, etc.), that, when well orchestrated, enable clearance of the invading pathogen. However, it is also hypothesized that activated PMN may possess harmful potential when these same functions are directed at otherwise normal host tissue, culminating in injury and organ damage (Figure 1 ). There is sub- Figure 1 . Proposed mechanisms of acute lung injury through hemorrhagic shock (HEM) "priming" for inflammation (Infl./red color)/apoptosis (Ao/ gray color)/injury, and "triggered" by a subsequent infectious insult: The resting lung (A) is primed by divergent inflammatory mediators released during an initial event (for example, shock, inflammation, etc.) that acts on a number of cells in the blood (MΦ: monocytes, PMN: neutrophils) and lung (EP: epithelial cells, EC: endothelial cells, AMΦ: alveolar macrophages) (B). These cells, in turn, stimulate, either separately or concomitantly, the pro-inflammatory response and/or the Ao of a small number of EP, both through Fas-FasL activation. The release of chemokines like MCP-1 then primes the AMΦ. When, at a later time, a subsequent inflammatory/infectious ('trigger') event takes place (C) the local EC, AMΦ, and/or EP become activated, release chemokines and activating agents that recruit the primed and now activated leukocytes (PMN, MΦ) to the lung (D). These activated leukocytes then transmigrate into the interstitium and alveoli where they perform their effector roles (in the absence of infection, the effector response may be solely injurious). In addition, they may propel the inflammatory/apoptotic response into a vicious cycle by further activating Fas through FasL on their cell surface (E). stantial evidence that the lung is particularly susceptible for PMN accumulation. In contrast to most other organs, where PMN sequestration occurs at post-capillary venules, pulmonary PMN retention takes place within the pulmonary capillaries, representing a complex interconnecting network of short capillary segments where the course from arteriole to venule crosses numerous alveolar walls and often includes more than 50 capillary segments. The blood in this complex network contains 50 times more PMN compared with most other vascular beds (reviewed in 18) .