Induction of histamine release from human skin mast cells by bradykinin analogs.
Induction of histamine release from human skin mast cells by bradykinin analogs.
复制标题
缓激肽类似物诱导人皮肤肥大细胞释放组胺。
DOI：
10.1016/0006-2952(89)90031-2
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发表时间：
1989
影响因子：
5.8
通讯作者：
Proud,D
中科院分区：
文献类型：
--
作者：
Lawrence,ID;Warner,JA;Cohan,VL;Lichtenstein,LM;Kagey-Sobotka,A;Vavrek,RJ;Stewart,JM;Proud,D
激肽是一种有效的促炎肽，可诱导啮齿动物肥大细胞释放组胺。我们检测了缓激肽、赖氨酸缓激肽和一系列激肽类似物引起人嗜碱性粒细胞、人肺肥大细胞和人皮肤肥大细胞释放组胺的能力。在0.1μM到1 mM的浓度范围内，缓激肽不能引起所研究的任何含有组胺的人类细胞释放组胺。Ly缓激肽对嗜碱性粒细胞和肺肥大细胞也无影响，但对人皮肤肥大细胞有微弱的促分泌剂作用，在10−5M时，可诱导细胞总组胺释放的5.5±3%(平均值±SD)。同样，当研究了16种新近开发的缓激肽拮抗剂时，这些化合物对嗜碱性粒细胞或肺肥大细胞没有影响，但所有16种化合物都能诱导皮肤肥大细胞释放剂量依赖的组胺。其释放过程与温度有关，在10−~5M浓度时，可诱导8~27%的组胺释放。尽管10−3M缓激肽或DES(Arg9)缓激肽可显著抑制拮抗剂诱导的组胺释放，但需要如此高浓度的这些多肽来抑制组胺释放，提示组胺释放不是由B1或B2kinin受体介导的。为了进一步了解组胺释放的机制，我们研究了缓激肽序列中具有单一氨基酸取代的一系列缓激肽类似物。将缓激肽序列中的Proline7替换为d-苯丙氨酸是激动素类似物转化为拮抗剂的基本改变，10−5M[dPhe7-Bradykinin]可引起8-10%的组胺释放。然而，其他缺乏拮抗活性的类似物，如[dPhe6]-Bradykinin和[LPhe7]-Bradykinin能够诱导同等水平的组胺释放。诱导组胺释放的能力似乎至少部分与芳香性有关，因为[bTrp6]-缓激肽和[dTrp7]-缓激肽比同等的[dPhe]-类似物诱导更多的组胺释放，在10−5m时导致大约20%的组胺释放。相比之下，[dAla7]-缓激肽是一种无效的刺激。综上所述，单一的氨基酸替代可以将缓激肽转化为人类皮肤肥大细胞的促分泌剂。激肽类似物能够诱导皮肤肥大细胞释放组胺，但不能诱导肺肥大细胞或嗜碱性粒细胞释放组胺，这强调了人类含有组胺的细胞的异质性。
Kinins are potent proinflammatory peptides that induce histamine release from rodent mast cells. We examined the ability of bradykinin, lysylbradykinin and a series of kinin analogs to cause histamine release from human basophils, human lung mast cells and human skin mast cells. At concentrations ranging from 0.1 μM to 1 mM, bradykinin failed to cause histamine release from any of the human histamine-containing cells studied. Lysylbradykinin was also without effect on basophils and lung mast cells, but was a weak secretagogue for human skin mast cells, inducing 5.5 ± 3% (mean ± SD) of total cellular histamine release at a concentration of 10−5M. Similarly, when sixteen recently developed bradykinin antagonists were examined, these compounds had no effect on basophils or lung mast cells but all sixteen induced dose-dependent histamine release from skin mast cells. The release process was temperature dependent and, at a concentration of 10−5M, the antagonists induced 8–27% histamine release. Although preincubation of cells with 10−3M bradykinin or des(Arg9) bradykinin significantly inhibited antagonist-induced histamine release, the requirement for such high concentrations of these peptides to cause inhibition suggested that histamine release is not mediated by either B1or B2kinin receptors. To understand further the mechanism of histamine release, we examined a series of bradykinin analogs with single amino acid substitutions in the bradykinin sequence. Replacement of proline7in the bradykinin sequence withd-phenylalanine is the essential change used to convert kinin analogs into antagonists, and 10−5M [dPhe7-bradykinin induced 8–10% histamine release. Other analogs, devoid of antagonist activity, however, such as [dPhe6]-bradykinin and [LPhe7]-bradykinin were able to induce equivalent levels of histamine release. The ability to induce histamine release appears to be related, at least in part, to aromaticity, since [bTrp6]-bradykinin and [dTrp7]-bradykinin induced greater amounts of histamine release than equivalent [dPhe]-analogs, causing approximately 20% histamine release at 10−5M. By contrast, [dAla7]-bradykinin was an ineffective stimulus. In summary, a single amino acid substitution can convert bradykinin into a secretagogue for human skin mast cells. The ability of kinin analogs to induce histamine release from skin mast cells, but not lung mast cells or basophils, emphasizes the heterogeneity of human histamine-containing cells.