Biochemical signals transmitted by Fc gamma receptors: triggering mechanisms of the increased synthesis of adenosine-3',5'-cyclic monophosphate mediated by Fc gamma 2a- and Fc gamma 2b- -receptors of a murine macrophage-like cell line (P388D1).
Biochemical signals transmitted by Fc gamma receptors: triggering mechanisms of the increased synthesis of adenosine-3',5'-cyclic monophosphate mediated by Fc gamma 2a- and Fc gamma 2b- -receptors of a murine macrophage-like cell line (P388D1).
复制标题
Fc γ 受体传递的生化信号：触发小鼠巨噬细胞样细胞系 (P388D1) 的 Fc γ 2a 和 Fc γ 2b 受体介导的腺苷 3,5-环单磷酸合成增加的机制。
作者：
T. Nitta;T. Suzuki
IgG2a 或 IgG2b 亚类单克隆抗绵羊红细胞抗体分别与 P388D1 细胞表面 Fc gamma 2aR3 或 Fc gamma 2bR 特异性结合，通过每种类型的 Fc gamma R 明显独特的机制，以大致相同的程度触发腺苷 3'5'-单磷酸 (cAMP) 的合成。 Fc gamma 2aR 似乎在与 IgG2a 抗体结合后直接触发腺苷酸环化酶系统，而不需要鸟嘌呤核苷酸结合 (G/F) 调节蛋白的参与，因为 Fc gamma 2aR 触发的 cAMP 合成在 30 分钟内达到最大值，并且不受解偶联剂 Mn++ 或添加三磷酸鸟苷 (GTP) 类似物 5'-鸟苷酰亚胺二磷酸的显着影响(Gpp(NH)p)。相比之下，Fc gamma 2bR 似乎通过产生前列腺素来间接刺激需要腺苷酸环化酶的 G/F 调节系统，因为 cAMP 合成（在 IgG2b 与 Fc gamma 2bR 结合后需要 90 分钟才能达到平台）完全被磷脂酶 A2 抑制剂（对溴苯甲酰溴）或环加氧酶抑制剂（吲哚美辛）抑制，被 Mn++ 部分抑制，并且被 Mn++ 略微增加。 Gpp(NH)p。此外，细胞松弛素 D 对吞噬过程的抑制增加了 Fc γ 2aR 介导的 cAMP 合成（2 微克/ml 时约 70%），但不影响 Fc γ 2bR 介导的 cAMP 合成。此外，我们的数据表明，Fc γ 2aR 和 Fc γ 2bR 介导的 cAMP 合成均独立于 β 肾上腺素能受体介导的腺苷酸环化酶系统刺激，因为 β 激动剂（异丙肾上腺素）或 β 拮抗剂（普萘洛尔）不会显着影响 EA 刺激产生的 cAMP 水平。
The specific binding of IgG2a or IgG2b subclass monoclonal anti-sheep erythrocyte antibodies to P388D1 cell surface Fc gamma 2aR3 or Fc gamma 2bR, respectively, triggered the synthesis of adenosine-3'5'-monophosphate (cAMP) to an approximately same extent by the mechanisms that are apparently unique for each type of Fc gamma Rs. Fc gamma 2aR appeared to trigger directly, upon binding of IgG2a antibodies, the adenylate cyclase system without requiring the participation of guanine nucleotide-binding (G/F) regulatory protein, because the Fc gamma 2aR-triggered cAMP synthesis, which reached maximum within 30 min, was not significantly affected by an uncoupler, Mn++ or by addition of guanosine triphosphate (GTP) analog, 5'-guanylylimidodiphosphate (Gpp(NH)p). In contrast, Fc gamma 2bR appeared to stimulate indirectly the G/F regulatory requiring-adenylate cyclase system by generating prostaglandins, since the cAMP synthesis, which required 90 min to reach plateau after binding of IgG2b to Fc gamma 2bR, was totally suppressed by phospholipase A2 inhibitor (p-bromophenacylbromide) or cyclo-oxygenase inhibitor (indomethacin), partially suppressed by Mn++, and slightly increased by Gpp(NH)p. Furthermore, the inhibition of phagocytic process by cytochalasin D increased cAMP synthesis mediated by Fc gamma 2aR (about 70% at 2 micrograms/ml), but did not affect Fc gamma 2bR-mediated cAMP synthesis. In addition, our data suggested that both Fc gamma 2aR- and Fc gamma 2bR-mediated cAMP synthesis are independent from beta-adrenergic receptor-mediated stimulation of the adenylate cyclase system, since either beta-agonist (isoproterenol) or beta-antagonist (propranolol) did not affect significantly the levels of cAMP produced in response to EA-stimulation.