Effect of Decay-accelerating Factor on LPS-induced Acute Lung Injury in the Rat

Complement activation has been implicated as a contributor to lung injury. Membrane-bound complement regulatory proteins, including decay-accelerating factor (DAF), control complement activation, thus mitigating complement-mediated injury. Their effect on lung injury remains unexplored. Using a DAF knockout rat model, we assessed the effect of DAF on the extent of lipopolysaccharide (LPS)-mediated acute lung injury (ALI) in rats.

Wild-type (WT) and DAF-knock out (Daf^-/- ) rats were injected intraperitoneally with a sublethal LPS dose. Following 16 h, protein and cytokine levels were assessed using immunohistochemistry/immunoblotting and ELISA, respectively.

LPS administration to WT rats caused histopathological lesions indicative of ALI and significantly increased infiltrating inflammatory cells, as well as total number of cells and interleukin (IL)-6 levels, in bronchoalveolar lavage fluid samples. DAF absence resulted in increased C3b levels in Daf^-/- control rats, compared with their WT controls. LPS administration to Daf^-/- rats exacerbated lung injury without an effect on C3b levels. Higher baseline tissue protein levels of the anaphylatoxin complement component 5a receptor 1 (C5aR1) were observed in Daf^-/- rats compared with WT whereas LPS administration to either group resulted in reduced levels of C5aR1, albeit not significant. DAF deficiency had no effect on baseline protein levels of CR1-related gene/protein Y (Crry) complement regulator, whereas LPS administration increased Crry protein levels to a similar extent in WT and Daf^-/- rats.

DAF deficiency increased baseline C3b and C5aR1 protein levels in lung tissue. LPS-induced inflammatory response and lung injury were augmented in Daf^-/- rats without further increase in C3b and in the absence of significant changes in the expression of membrane-bound complement regulatory proteins, DAF and Crry, or the anaphylatoxin receptor C5aR1.