Phospholipase A₂ activity in dystrophinopathies

Phospholipase A₂ activity in human muscle with or without dystrophin abnormality was studied. The results showed an increased phospholipase A₂ activity in Duchenne muscular dystrophy (DMD) patients (1160 ± 160, P <0,01) compared to controls (<200 U mg^-1). DMD fetal muscle showed normal levels, but levels then increased dramatically postnatally. Highest levels were found at 5 yr of age (10 times normal) and then declined to 1.5-2 times normal by age 10. Steroid treatment did not change the phospholipase A₂ levels significantly. In patients with abnormal dystrophin, i.e. Becker muscular dystrophy, phospholipase A₂ activity was increased in the age group 3-15 (920 ± 230 U mg^-1, P <0.01), while older patients (17-49) showed a non-significant (220 ± 60 U mg^-1) increase. The lack of phospholipase A₂ activation in fetuses with DMD, indicates that activation is not a direct consequence of dystrophin deficiency. Phospholipase A₂ activity has been shown to be connected to the formation of several inflammatory mediators such as prostaglandins, leukotriens, platelet activating factor and lysophospholipids. Phospholipase A₂ activation may therefore play an important role in the development of inflammation and necrosis, with subsequent fibrosis and massive loss of muscle function, which develops in Duchenne and Becker muscular dystrophy.