Deletion of secretory group v phospholipase A2 attenuates cell migration and airway hyperresponsiveness in immunosensitized mice
Deletion of secretory group v phospholipase A2 attenuates cell migration and airway hyperresponsiveness in immunosensitized mice
复制标题
DOI：
10.4049/jimmunol.179.7.4800
复制
发表时间：
2007-10-01
影响因子：
4.4
通讯作者：
Leff, Alan R.
中科院分区：
文献类型：
--
作者：
Munoz, Nilda M.;Meliton, Angelo Y.;Leff, Alan R.
我们研究了 V 族磷脂酶 A(2) (gVPLA(2)) 在 OVA 诱导的 C57BL/6 小鼠炎症细胞迁移和气道高反应性 (AHR) 中的作用。重复的过敏原激发诱导气道中 gVPLA(2) 的生物合成。通过气雾剂，gVPLA(2) 引起盐水处理小鼠气道阻力的剂量相关增加；在过敏小鼠中，gVPLA(2) 导致持续性气道狭窄。 IIa 组磷脂酶 A(2)（gVPLA(2) 的密切同源物）和 W31A（活性降低的失活 gVPLA(2) 突变体）均不会导致免疫敏感小鼠气道狭窄。在 OVA 攻击之前，用 MCL-3G1（一种针对 gVPLA(2) 的阻断抗体）进行预处理，可完全阻断 gVPLA(2) 诱导的细胞迁移和气道狭窄，表现为支气管肺泡灌洗液中迁移白细胞的减少和气道阻力的降低。我们还评估了乙酰甲胆碱激发引起的非特异性 AHR 是否是由免疫致敏小鼠的常驻气道细胞分泌的 gVPLA(2) 引起的。 MCL-3G1 还可以阻断过敏小鼠中醋甲胆碱诱导的气道支气管收缩。 MCL-3G1 对支气管收缩的阻断作用在过敏性 pla2g5(-/-) 小鼠中得到复制，该小鼠缺乏编码 gVPLA(2) 的基因。 pla2g4(-/-) 小鼠中gVPLA(2) 引起的支气管收缩与pla2g4(+/+) 小鼠中的支气管收缩相当。我们的数据表明，gVPLA(2) 是 AHR 发展和免疫敏化期间细胞迁移调节中的关键信使酶，通过独立于 IV 族磷脂酶 A(2) 的途径。
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 challenge was elicited by gVPLA(2) secreted from resident airway cells of immune-sensitized mice. MCL-3G1 also blocked methacholine-induced airway bronchoconstriction in allergic mice. Blockade of bronchoconstriction by MCL-3G1 was replicated in allergic pla2g5(-/-) mice, which lack the gene encoding gVPLA(2). Bronchoconstriction caused by gVPLA(2) in pla2g4(-/-) mice was comparable to that in pla2g4(+/+) mice. Our data demonstrate that gVPLA(2) is a critical messenger enzyme in the development of AHR and regulation of cell migration during immunosensitization by a pathway that is independent of group IV aphospholipase A(2).