CYCLIC ADENOSINE MONOPHOSPHATE ELEVATION--EFFECTS ON NEUTROPHIL MOTILITY

环磷酸腺苷升高--对中性粒细胞运动的影响

• 批准号: 3811074
• 负责人: L HARVATH
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3811074
• 关键词: adenylate cyclase; cell migration; chemoattractants; chemotaxis; cyclic AMP; forskolin; human tissue; isoproterenol; leukotrienes; neutrophil; phosphodiesterase inhibitors; prostaglandin E

Neutrophils (PMNs) treated with cyclic AMP elevating agents were evaluated for to N-formyl-methionyl-leucyl-phenylalanine (FMLP) and leukotriene B(4) (LTB(4)). Prostaglandin E(1) (PGE(1)) and isoproterenol, increased PMN cyclic in AMP production and inhibited chemotaxis to both FMLP and LTB(4). In contrast, forskolin, which activates adenylate cyclase directly, inhibited chemotaxis to FMLP but not to LTB(4). The phosphodiesterase inhibitor, 3-isobutyl-1 -methylxanthine (IBMX), was, required for inhibition of PMN chemotaxis to FMCP by forskolin, PGE,, and isoproterenol. Isoproterenol and PGE, inhibited PMN chemotaxis to LTB4 in the absence of IBMX and chemotaxis was further inhibited in the presence of IBMX. PMN cyclic AMP levels were stimulated 2-3-fold with isoproterenol, 6-10-fold with PGE1, and 5-7-fold with forskolin over basal levels in the presence of IBMX. These observations demonstrate that total cellular cyclic AMP concentration is not-correlated with inhibition of PMN chemotaxis to all stimuli; forskolin, which increased cyclic AMP 5-7-fold over basal levels, did not inhibit chemotaxis to LTB4, Whereas isoproterenol, which increased cyclic AMP only 2-3-fold over basal levels, inhibited -chemotaxis to LTB4- PMN cyclic AMP extrusion was determined under basal conditions and in the presence of PGE1, isoproterenol, or forskolin. PMNs extruded cyclic AMP under all conditions examined. Results of this study were presented at the 1990 FASEB Meetings, April 1-5, 1990 in Washington, D.C. A manuscript describing this work has been submitted.

评估用环 AMP 升高剂处理的中性粒细胞 (PMN) 用于 N-甲酰基-甲硫氨酰-亮氨酰-苯丙氨酸 (FMLP) 和白三烯 B(4) （LTB（4））。 前列腺素 E(1) (PGE(1)) 和异丙肾上腺素，PMN 增加 AMP 生成中呈环状，并抑制对 FMLP 和 LTB 的趋化性(4)。 相比之下，毛喉素直接激活腺苷酸环化酶， 抑制对 FMLP 的趋化作用，但不抑制对 LTB 的趋化作用(4)。 磷酸二酯酶 抑制剂 3-异丁基-1-甲基黄嘌呤 (IBMX) 是 毛喉素、PGE 和异丙肾上腺素抑制 PMN 对 FMCP 的趋化性。 异丙肾上腺素和 PGE 在缺乏的情况下抑制 PMN 对 LTB4 的趋化性 IBMX 的存在进一步抑制了 IBMX 和趋化性。中性粒细胞网络 环AMP水平被异丙肾上腺素刺激2-3倍，6-10倍 与 PGE1 相比，在存在以下物质的情况下，与福司可林相比，其水平是基础水平的 5-7 倍 IBMX。这些观察结果表明，总细胞环 AMP 浓度与对所有 PMN 趋化性的抑制不相关 刺激；毛喉素，使环 AMP 比基础水平增加 5-7 倍， 不抑制 LTB4 的趋化性，而异丙肾上腺素会增加 环AMP仅比基础水平高2-3倍，抑制-LTB4-趋化性- PMN 环 AMP 挤出是在基础条件下和在 存在 PGE1、异丙肾上腺素或毛喉素。 PMN 挤压环 AMP 在所有检查条件下。 这项研究的结果已在 4 月 1 日至 5 日举行的 1990 年 FASEB 会议上公布， 1990 年在华盛顿特区。描述这项工作的手稿已被 已提交。