Decreased respiratory burst activity in neonatal bovine neutrophils stimulated by protein kinase C agonists.
Newborn calves have a high susceptibility to bacterial infections, which may be related to the impaired neutrophil defense functions in newborns. The oxygen-dependent production of the free radical superoxide anion (O2-) represents an important part of the leukocyte respiratory burst central to neutrophil-directed defenses against bacterial infection. Because protein kinase C (PKC) activation is considered to be an important step in the signal transduction pathway for the O2- generating system, we compared O2- production by newborn and adult bovine neutrophils stimulated with 3 different PKC agonists. When the phorbol ester phorbol 12-myristate 13-acetate (PMA) was used, PKC-dependent O2- generation from newborn neutrophils was significantly reduced (P less than 0.01) for all concentrations of PMA tested (10, 100, and 500 ng/ml). In addition, newborn neutrophils had a significantly (P less than 0.01) reduced lag time for O2- generation. Similar significantly (P less than 0.01) reduced O2- generation from newborn neutrophils was observed with an additional phorbol ester (phorbol 12,13-dibutyrate); lag times were not calculated for phorbol 12,13-dibutyrate. When O2- generation was stimulated with a synthetic diacylglycerol analogue (1,2-dioctanoyl-sn-glycerol), less O2- was generated from both adult and newborn neutrophils than was obtained with the phorbol esters, and newborn neutrophils produced significantly (P less than 0.01) less O2- only at 50 microM 1,2-dioctanoyl-sn-glycerol.(ABSTRACT TRUNCATED AT 250 WORDS)
Doré
M
M
Department of Pathology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
Slauson
D O
DO
Neilsen
N R
NR
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D002417:Cattle / Q000276:immunology*; D002478:Cells, Cultured; D004075:Diglycerides / Q000138:chemical synthesis / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007546:Isoquinolines / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000494:pharmacology*; D013449:Sulfonamides; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004075:Diglycerides; D007546:Isoquinolines; D010879:Piperazines; D013449:Sulfonamides; C044295:1,2-dioctanoylglycerol; D013481:Superoxides; D015240:Phorbol 12,13-Dibutyrate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate