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).