A proposed model for the current understanding of C5a-mediated inflammatory pathophysiology of acute lung injury is depicted in Figure 2 . Anaphylatoxin C5a has been shown to induce the early release of proinflammatory cytokines by alveolar macrophages, such as TNF and interleukin (IL)-1β [104] . Interaction of endothelial adhesion molecules (e.g. ICAM-1) with their corresponding receptors on neutrophils (e.g. CD11b/ CD18) leads to adhesion and transmigration of neutrophils into the alveoli [104] . Furthermore, release of TNF and IL-1β can also function in an autocrine way and activate alveolar macrophages to generate chemokines [112] . Among these, the different chemokines have been shown to further mediate neutrophil infiltration [113] . Activated neutrophils, alveolar macrophages and epithelial cells release reactive oxygen species and proteinases that cause diffuse alveolar and microvascular damage, thus exacerbating acute lung injury [111] .