TY - JOUR T1 - cPLA2α plays a role in neutrophilic inflammatory response in mice induced by tobacco smoke exposure JF - European Respiratory Journal JO - Eur Respir J VL - 42 IS - Suppl 57 SP - P528 AU - Hiroo Wada AU - Masuo Nakamura AU - Manabu Higaki AU - Naonori Uozumi AU - Yoshihiro Kita AU - Motonao Nakamura AU - Takao Shimizu AU - Hajime Takizawa AU - Hajime Goto Y1 - 2013/09/01 UR - http://erj.ersjournals.com/content/42/Suppl_57/P528.abstract N2 - INTRODUCTIONLipid mediators possess a strong chemotactic activity, and it is thus hypothesized that they also play a pathogenic role in neutrophilic inflammatory responses induced by cigarette smoke (CS) exposure. To address this, cPLA2α deficient mice were exposed to CS and then analyzed.METHODScPLA2 deficient mice and litter-mate wild type mice were both exposed to CS for 9 days. Brocho-alveolar lavage (BAL) was performed and the fluid was collected. Cell counts, as well as their differentials, were determined. Furthermore, the protein levels of MMP-9 and keratinocyte-derived chemokine (KC), a murine homologue of human IL-8/CXCL-8, were measured in BAL fluid, using enzyme-linked immunosorbent assay (ELISA).RESULTSAlthough the total cell counts in cPLA2α deficient mice and those in wild type mice were mostly same in number, neutrophil counts were significantly lower in cPLA2α deficient mice than in wild type by 69.7% reduction (p < 0.05). The KC protein levels in BAL fluid were 6.9+/-3.3 pg/mL in cPLA2α deficient mice, significantly lower than those in wild type mice, 11.0+/-3.8pg/mL (p < 0.05). MMP-9 levels in BAL fluid were 0.2+/-0.2ng/mL in in cPLA2 deficient mice, significantly lower than those in wild type mice, 0.6+/-0.2 (p < 0.05).DISCUSSIONOur result demonstrated that reduction in KC production was in part dependent on lack of lipid mediators associated with cPLA2α, and that both attenuated regulation of KC and lipid mediators further lead to reduction in neutrophil recruitment and MMP-9 production in the lung. It is thus implicated that induction of cPLA2α in the lung plays a role in neutrophilic inflammation as well as remodeling process, induced by CS exposure. ER -