Role of Secretory Phospholipase A2 in CNS Inflammation: Implications in Traumatic Spinal Cord Injury

Abstract

Secretory phospholipases A(2) (sPLA(2)s) are a subfamily of lipolytic enzymes which hydrolyze the acyl bond at the sn-2 position of glycerophospholipids to produce free fatty acids and lysophospholipids. These products are precursors of bioactive eicosanoids and platelet-activating factor (PAF). The hydrolysis of membrane phospholipids by PLA(2) is a rate-limiting step for generation of eicosanoids and PAF. To date, more than 10 isozymes of sPLA(2) have been found in the mammalian central nervous system (CNS). Under physiological conditions, sPLA(2)s are involved in diverse cellular responses, including host defense, phospholipid digestion and metabolism. However, under pathological situations, increased sPLA(2) activity and excessive production of free fatty acids and their metabolites may lead to inflammation, loss of membrane integrity, oxidative stress, and subsequent tissue injury. Emerging evidence suggests that sPLA(2) plays a role in the secondary injury process after traumatic or ischemic injuries in the brain and spinal cord. Importantly, sPLA(2) may act as a convergence molecule that mediates multiple key mechanisms involved in the secondary injury since it can be induced by multiple toxic factors such as inflammatory cytokines, free radicals, and excitatory amino acids, and its activation and metabolites can exacerbate the secondary injury. Blocking sPLA(2) action may represent a novel and efficient strategy to block multiple injury pathways associated with the CNS secondary injury. This review outlines the current knowledge of sPLA(2) in the CNS with emphasis placed on the possible roles of sPLA(2) in mediating CNS injuries, particularly the traumatic and ischemic injuries in the brain and spinal cord.