Oxatomide inhibits synthesis and release of platelet-activating factor in human neutrophils.
Effect of oxatomide on release and production of platelet-activating factor (PAF) in neutrophils obtained from asthmatic and non-asthmatic patients was investigated. Neutrophils were preincubated with or without oxatomide and stimulated with N-formyl-L-methionyl-L-leucyl-L-phenylalanine (f-MLP, 10 microM) for 15 min. PAF activity was detected by aggregation of washed guinea pig platelets. PAF activity released from asthmatic neutrophils without preincubation of oxatomide was 7.97[0.22] (mean[SEM], ng/10(7) cells) in supernatants and 33.4[0.26] in cell pellets. After preincubation with 10(-8), 10(-6), and 10(-4) M of oxatomide, PAF activity reduced to 6.77[0.37] (mean[SEM], ng/10(7) cells), 3.99[0.25], and 0.96[0.05] (n = 15) in the supernatants, and 22.4[0.31], 16.7[0.22], and 6.35[0.11] (n = 15) in the cell pellets, respectively. PAF activity in non-asthmatic neutrophils without preincubation of oxatomide was 6.35[0.12] (mean[SEM], ng/10(7) cells) in supernatants and 27.9[0.25] in cell pellets. After preincubation with 10(-8), 10(-6), and 10(-4) M of oxatomide, PAF activity reduced to 5.02[0.16] (mean [SEM], ng/10(7) cells), 3.96[0.11], and 0.94[0.03] (n = 10) in the supernatants, and 28.4[0.69], 13.78[0.17], and 2.88[0.27] (n = 10) in the cell pellets, respectively. Our results showed that preincubation with oxatomide caused a dose-dependent inhibition of intra- and extracellular PAF activity from asthmatic and non-asthmatic neutrophils in the same manner.
Shindo
K
K
First Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama, Japan.
Fukumura
M
M
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001249:Asthma / Q000097:blood; D002457:Cell Extracts / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000008:administration & dosage / Q000494:pharmacology; D009504:Neutrophils / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000032:analysis / Q000187:drug effects / Q000378:metabolism* / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D018927:Anti-Asthmatic Agents; D002457:Cell Extracts; D010879:Piperazines; D010972:Platelet Activating Factor; C037145:1-hexadecyl-2-acetyl-glycero-3-phosphocholine; D009240:N-Formylmethionine Leucyl-Phenylalanine; C015408:oxatomide