Functional expression of H4 histamine receptor in human natural killer cells, monocytes, and dendritic cells
Functional expression of H4 histamine receptor in human natural killer cells, monocytes, and dendritic cells
复制标题
DOI：
10.4049/jimmunol.179.11.7907
复制
发表时间：
2007-12-01
影响因子：
4.4
通讯作者：
Maghazachi, Azzam A.
中科院分区：
文献类型：
--
作者：
Damaj, Bassam B.;Becerra, Cecilia Barrena;Maghazachi, Azzam A.
我们在这里描述了H4组胺受体在先天免疫系统细胞中的蛋白表达，这些细胞包括NK细胞、单核细胞和树突状细胞（DC）。抗H4 R特异性染色透化NK细胞、THP-1克隆15单核细胞和DC。通过将抗H4 R Ab与其相应肽孵育来抑制这种结合。组胺诱导NK细胞、THP-1克隆15细胞和DC具有高亲和力的趋化性。NK细胞、THP-1克隆15细胞和DC的ED 50趋化效应分别为5 nM、6.8 nM和2.7 nM。H3 R/H4 R拮抗剂硫代哌丁胺可抑制组胺诱导的所有这些细胞的趋化性。然而，组胺不能诱导NK细胞和THP-1克隆15细胞中[Ca 2 +]（i）的动员，但可诱导DC中的钙流。使用检测NK细胞介导的细胞溶解的新方法，观察到NK细胞有效地溶解K562靶细胞，并且组胺不影响这种NK细胞活性。综上所述，这是NK细胞中H4受体蛋白表达的首次证明。此外，组胺对NK细胞和THP-1细胞的趋化作用的结果是新颖的。这些结果可能揭示了先天免疫臂细胞在炎症部位的共定位。它们对于开发靶向H4 R的药物以治疗各种疾病也很重要，例如自身免疫和免疫缺陷疾病。
We describe here the protein expression of H4 histamine receptor in cells of the innate immune system, which include NK cells, monocytes, and dendritic cells (DCs). Anti-H4R specifically stained permeabilized NK cells, THP-1 clone 15 monocytes, and DCs. This binding was inhibited by incubating anti-H4R Ab with its corresponding peptide. Histamine induced NK cells, THP-1 clone 15 cells, and DCs chemotaxis with high affinity. The ED50 chemotactic effect was 5 nM, 6.8 nM, and 2.7 nM for NK cells, THP-1 clone 15 cells, and DCs, respectively. Thioperamide, an H3R/H4R antagonist, inhibited histamine-induced chemotaxis in all these cells. However, histamine failed to induce the mobilization of [Ca2+](i) in NK cells and THP-1 clone 15 cells, but it induced calcium fluxes in DCs. Using a new method of detecting NK cell-mediated cytolysis, it was observed that NK cells efficiently lysed K562 target cells and that histamine did not affect this NK cell activity. In summary, this is the first demonstration of the protein expression of H4 receptor in NK cells. Also, the results of the chemotactic effects of histamine on NK cells and THP-1 cells are novel. These results may shed some light on the colocalization of cells of innate immune arm at sites of inflammation. They are also important for developing drugs that target H4R for the treatment of various disorders, such as autoimmune and immuno-deficient diseases.