Excess formation of lysophosphatidic acid with age inhibits myristic acid-induced superoxide anion generation in intact human neutrophils

• Published in: FEBS letters 1996-09, Vol.394 (2), p.149-152
• Main Authors: Ito, Yoshikazu, Ponnappan, Usha, Lipschitz, David A.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aging; Aging - metabolism; arachidonic acid; Arachidonic Acid - metabolism; Calcium - pharmacology; diacylglycerol; FMLP; Humans; inositol trisphosphate; Ionomycin - pharmacology; IP3; LPA; lysophosphatidic acid; Lysophospholipids - metabolism; Myristic Acid; Myristic Acids - pharmacology; n-formyl-methionyl-leucyl-phenylalanine; Neutrophils - drug effects; Neutrophils - metabolism; Oxidative burst; Phosphatidic acid; Phosphatidic Acids - metabolism; Phospholipase; phospholipase A2; phospholipase C; phospholipase D; Phospholipases A - metabolism; Phospholipases A2; PLA2; PLC; PLD; Saturated fatty acid; Superoxides - metabolism; thin layer chromatography; TLC
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(96)00937-4

A superoxide anion generation rate upon exposure to myristate of 1.93 ± 0.34 nmol/min/10 6 cells in neutrophils from elderly human donors was significantly less than a value of 3.02 ± 0.48 nmol/min/10 6 neutrophils from young donors. Myristate activation resulted in equal increases of AA in both the young and the old indicating no effect of aging on the PLA 2 pathway to response. By contrast, the PLD-induced generation of PA was significantly higher in the old than in the young. In addition, myristate induced a significant age-related enhancement in LPA generation, in the old but not in the young. The mass of LPA generated following activation was 3.5 nmol/ 2.5 × 10 7cells/ml in the young while in the old it averaged 7.0 nmol/2.5 × 10 7 cells/ml. The inhibitory effects of LPA may explain the age-related impaired ability to generate superoxide anion following activation by myristate.