Do porins inhibit the macrophage phagocyting activity by stimulating the adenylate cyclase?

A Di Donato, G F Draetta, G Illiano, M A Tufano, L Sommese, F Galdiero
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Abstract

Porins interact with macrophage membranes and inhibit their phagocyting activity. We have tested the porin effect on a biologically relevant membrane-bound enzymic activity, the adenylate cyclase system, which appears to be stimulated both in the presence of Mn2+ and Mg2+ or Mg2+ + Gpp(NH)p. Moreover, for mice macrophages incubated in the presence of porins, there is an increase in the intracellular cAMP content after 5 min of incubation, with a maximum after 15 min of incubation. The results shown suggest that the porin effects on the adenylate cyclase can represent the molecular basis of the porin-dependent inhibition of the macrophages phagocytosis. Our point of view, which proposes a cAMP role in inhibiting the phagocyting activity in macrophages, is supported also by the results of the experiments carried out in the presence of both dibutyryl-cAMP or aminophylline. The phagocyting activity is inhibited in all cases and independently of the bacteria to be phagocyted.

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孔蛋白是否通过刺激腺苷酸环化酶抑制巨噬细胞的吞噬活性?
孔蛋白与巨噬细胞膜相互作用,抑制其吞噬活性。我们已经测试了孔蛋白对生物相关膜结合酶活性的影响,腺苷酸环化酶系统,在Mn2+和Mg2+或Mg2+ Gpp(NH)p存在下似乎都受到刺激。此外,对于存在孔蛋白孵育的小鼠巨噬细胞,在孵育5 min后细胞内cAMP含量增加,在孵育15 min后达到最大值。结果表明,孔蛋白对腺苷酸环化酶的作用可能代表了孔蛋白依赖性巨噬细胞吞噬抑制的分子基础。我们提出cAMP在抑制巨噬细胞吞噬活性中的作用,这一观点也得到了在二丁基cAMP或氨茶碱存在下进行的实验结果的支持。在所有情况下,吞噬活性都受到抑制,并且与被吞噬的细菌无关。
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Calmodulin is required for a full activation of the calcium slow channels in heart cells. The escape of cyclic AMP from dog thyroid slices exposed to positive and negative regulators. Do porins inhibit the macrophage phagocyting activity by stimulating the adenylate cyclase? Kinetic evidence indicating separate stimulatory and inhibitory prostaglandin receptors on platelet membranes. A micromethod for the quantitation by radioimmunoassay of cyclic AMP in samples containing immuno-cross reactive compounds and other interfering substances.
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