Interleukin-1 upregulates anaphylatoxin receptors on mononuclear cells.
Interleukin-1 upregulates anaphylatoxin receptors on mononuclear cells.
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DOI：
10.1016/j.surg.2003.09.010
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发表时间：
2004-05
期刊：
影响因子：
3.8
通讯作者：
T. Takabayashi;S. Shimizu;B. D. Clark;M. Beinborn;J. F. Burke;J. Gelfand
中科院分区：
文献类型：
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作者：
T. Takabayashi;S. Shimizu;B. D. Clark;M. Beinborn;J. F. Burke;J. Gelfand
在创伤、大手术或感染过程中产生的过敏毒素C3a和C5a是有效的促炎介质，可增加白细胞介素（IL-1）细胞因子的合成。我们研究了IL-1对单核细胞中过敏毒素受体表达的影响。方法采用人单核细胞系MONO-MAC-6。采用竞争结合法检测C3a和C5a结合位点。通过逆转录-聚合酶链反应分析C3a和C5a受体的信使RNA水平。测定C3a和C5a对胞浆内游离Ca2+浓度（[Ca2+]i）的影响。结果MONO-MAC-6细胞中C3a和C5a的基础结合位点分别为10900 C3aR/细胞（Kd=2.0 nmol/L）和8700 C5aR/细胞（Kd=0.9 nmol/L）。IL-1α增加C3a（增加61%，P < 0.01）和C5a（增加71%，P < 0.001）的位点。在il -1α刺激的细胞中，C3aR和C5aR信使RNA水平也升高。受体偶联到功能反应，这是由C3a-或c5a诱导的[Ca2+]i增加所证明的。IL-1受体拮抗剂可阻断IL-1α对过敏毒素受体的上调作用。结论IL-1与过敏毒素可能通过单核细胞和巨噬细胞增强促炎作用。虽然C3a和C5a可以增加IL-1的单核细胞产生，但IL-1增加了这些过敏毒素受体的单核细胞表达，进一步放大了炎症。
BACKGROUNDThe anaphylatoxins, C3a and C5a, that are generated during trauma, major surgery, or infection are potent proinflammatory mediators that increase interleukin (IL-1) cytokine synthesis. We investigated the effects of IL-1 on anaphylatoxin receptor expression in monocytes.METHODSA human monocytic cell line, MONO-MAC-6, was used. C3a and C5a binding sites were assayed by competitive binding. Levels of messenger RNA for the C3a and C5a receptors were analyzed by reverse transcriptase-polymerase chain reaction. Changes of free cytosolic Ca2+concentration ([Ca2+]i) in response to C3a and C5a were measured.RESULTSBasal MONO-MAC-6 cell sites for C3a and C5a binding were 10,900 C3aR/cell (Kd=2.0 nmol/L), 8700 C5aR/cell (Kd=0.9 nmol/L). IL-1α increased sites for both C3a (61% increase; P < .01) and C5a (71% increase; P < .001). Levels of C3aR and C5aR messenger RNA also increased in IL-1α-stimulated cells. Receptors were coupled to functional responses, which were demonstrated by C3a- or C5a-induced [Ca2+]i increases. IL-1 receptor antagonist blocked the effects of IL-1α upregulation of anaphylatoxin receptors.CONCLUSIONThese results suggest that there is an additional link between IL-1 and anaphylatoxins to amplify proinflammatory effects through monocytes and macrophages. Although C3a and C5a can increase the monocyte production of IL-1, IL-1 increases monocyte expression of receptors for these anaphylatoxins, which further amplifies inflammation.