AbstractSecreted phospholipases A2(sPLA2s) are well known for their contribution in the biosynthesis of inflammatory eicosanoids. These enzymes also participate in the inflammatory process by regulating chemokine production and protein expression of adhesion molecules. The majority of sPLA2isoforms are up‐regulated by proinflammatory stimuli such as bacterial lipopolysaccharide (LPS), which predominantly increases the expression of group V sPLA2(sPLA2‐V). Furthermore, it has recently been shown that sPLA2‐V is a critical messenger in the regulation of cell migration during allergic airway responsiveness. Herein, we investigated the effect of sPLA2‐V on LPS‐mediated leukocyte recruitment and its capacity to modulate adhesion molecule expression. We conducted our study in the murine air pouch model, using sPLA2‐V null mice (sPLA2‐V−/−) and control wild‐type (WT) littermates. We observed that LPS (1 µg/ml)‐mediated leukocyte emigration in sPLA2‐V−/−was attenuated by 52% and 86% upon 6 and 12 h of treatment respectively, as compared to WT mice. In WT mice, treatment with the cell‐permeable sPLA2inhibitor (12‐epi‐scalaradial; SLD) reduced LPS‐mediated leukocyte recruitment by 67%, but had no additional inhibitory effect in sPLA2‐V−/−mice. Protein analyses from the air pouch skin were carried out upon LPS‐challenge, and the expression of intercellular adhesion molecule (ICAM)‐1 and vascular cell adhesion molecule (VCAM)‐1 were both significantly reduced in sPLA2‐V−/−mice as compared to control WT mice. Together, our data demonstrate the role of sPLA2‐V in LPS‐induced ICAM‐1 and VCAM‐1 protein overexpression and leukocyte recruitment, supporting the contribution of sPLA2‐V in the development of inflammatory innate immune responses. J. Cell. Physiol. 224:127–134, 2010 © 2010 Wiley‐Liss, Inc.