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We investigated the role of group V phospholipase A 2 (gVPLA 2) in OVA-induced inflammatory cell migration and airway hyperresponsiveness (AHR) in C57BL/6 mice. Repeated allergen challenge induced biosynthesis of gVPLA 2 in airways. By aerosol, gVPLA 2 caused dose-related increase in airway resistance in saline-treated mice; in allergic mice, gVPLA 2 caused persistent airway narrowing. Neither group IIa phospholipase A 2, a close homolog of gVPLA 2, nor W31A, an inactive gVPLA 2 mutant with reduced activity, caused airway narrowing in immune-sensitized mice. Pretreatment with MCL-3G1, a blocking Ab against gVPLA 2, before OVA challenge blocked fully gVPLA 2-induced cell migration and airway narrowing as marked by reduction of migrating leukocytes in bronchoalveolar lavage fluid and decreased airway resistance. We also assessed whether nonspecific AHR caused by methacholine …