Nagata S, Kebo D K, Kunkel S, Glovsky M M
Asthma and Allergy Center, Huntington Hospital, Pasadena, Calif. 91105.
Int Arch Allergy Immunol. 1992;97(3):194-9. doi: 10.1159/000236118.
The effect of adenylate cyclase activators on C5a- and f-Met-Leu-Phe-induced human neutrophil aggregation, enzyme release and superoxide production was investigated. C5a-stimulated superoxide production was markedly inhibited by adenylate cyclase activators, and the order of potency was PGE1 greater than isoproterenol greater than epinephrine greater than PGF2 alpha, which correlated with intracellular cAMP levels. However, neutrophil aggregation was inhibited by PGE1, PGE2, isoproterenol and epinephrine only at concentrations greater than 10(-6) M. Lysozyme release was inhibited only via PGEs in the presence of the phosphodiesterase inhibitor, methylisobutylxanthine. These results suggest that in the human neutrophil: (1) C5a-induced superoxide production is more sensitive to regulation by cAMP than neutrophil aggregation or enzyme release, and (2) the type of receptor occupied as well as the threshold level of cAMP are important in the regulation of neutrophil aggregation and enzyme release stimulated by C5a.
研究了腺苷酸环化酶激活剂对C5a和f-甲硫氨酰-亮氨酰-苯丙氨酸诱导的人中性粒细胞聚集、酶释放和超氧化物生成的影响。腺苷酸环化酶激活剂显著抑制C5a刺激的超氧化物生成，其效力顺序为前列腺素E1大于异丙肾上腺素大于肾上腺素大于前列腺素F2α，这与细胞内cAMP水平相关。然而，仅在浓度大于10(-6)M时，前列腺素E1、前列腺素E2、异丙肾上腺素和肾上腺素才抑制中性粒细胞聚集。在磷酸二酯酶抑制剂甲基异丁基黄嘌呤存在的情况下，仅通过前列腺素类物质抑制溶菌酶释放。这些结果表明，在人中性粒细胞中：(1)C5a诱导的超氧化物生成比中性粒细胞聚集或酶释放对cAMP调节更敏感，(2)被占据的受体类型以及cAMP的阈值水平在调节C5a刺激的中性粒细胞聚集和酶释放中很重要。
