Excess formation of lysophosphatidic acid with age inhibits myristic acid-induced superoxide anion generation in intact human neutrophils.
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 PLA2 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 x 10(7) cells/ml in the young while in the old it averaged 7.0 nmol/2.5 x 10(7) cells/ml. The inhibitory effects of LPA may explain the age-related impaired ability to generate superoxide anion following activation by myristate.
Ito
Y
Y
Department of Medicine, University of Arkansas for Medical Sciences and John L. McClellan Memorial Veterans Hospital, Little Rock 72205, USA.
Ponnappan
U
U
Lipschitz
D A
DA
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D008246:Lysophospholipids / Q000378:metabolism*; D019814:Myristic Acid; D009227:Myristic Acids / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D013481:Superoxides / Q000378:metabolism*
D008246:Lysophospholipids; D009227:Myristic Acids; D010712:Phosphatidic Acids; D019814:Myristic Acid; D013481:Superoxides; D016718:Arachidonic Acid; D015759:Ionomycin; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium