内源性组胺和 H1R、H2R 激动剂和拮抗剂对体内免疫球蛋白产生的调节。
Modulation of in vivo immunoglobulin production by endogenous histamine and H1R and H2R agonists and antagonists.
机构信息
Department of Biochemistry, Faculty of Medicine, Jawaharlal Nehru Medical College & Hospital, Aligarh Muslim University, Aligarh-202002, India.
出版信息
Pharmacol Rep. 2010 Sep-Oct;62(5):917-25. doi: 10.1016/s1734-1140(10)70352-2.
The present study was designed to delineate the immunomodulatory role of histamine receptors (H1R and H2R) and their antibody generation in a rabbit model. Six groups containing 18 rabbits each received either vehicle (sterile distilled water, 1 ml/kg x b.i.d), histamine (100 μg/kg x b.i.d.), H1R agonist (HTMT, 10 μg/kg x b.i.d.), H2R agonist (amthamine, 10 μg/kg x b.i.d.), H1R antagonist (pheniramine, 10 mg/kg x b.i.d.) or H2R antagonist (ranitidine, 10 mg/kg x b.i.d.). All animals were subsequently immunized with an intravenous injection of sheep red blood cells (SRBC). Estimations of total serum immunoglobulins (Igs), immunoglobulin M (IgM) and immunoglobulin G (IgG) were performed by ELISA and hemagglutination assay (HA) at days 0 (pre-immunization), 7, 14, 21, 28 and 58 (post-immunization). Both the ELISA and the HA showed similar production of Igs, IgM and IgG but the results were found comparatively more significant by ELISA as opposed to HA. Results showed that histamine could influence a detectable antibody response to SRBC early (i.e., at day 7), which lasted until day 58. Immunomodulatory processes showed suppression of an Ig generation in the H1R-antagonist group with enhancement in the H2R-antagonist group. The H1R-agonist group showed an increased Ig production in comparison to the H2R-agonist group. The IgM production was inhibited in the H1R-antagonist group as compared to the H2R-antagonist group, and it was also suppressed in H1R-agonist group as compared to H2R-agonist group. IgG production was inhibited in the H1R-antagonist group as opposed to the H2R-antagonist group. In contrast, the H1R-agonist group increased IgG production as compared to the H2R-agonist group. All the results were found to be statistically significant (p < 0.05 or p < 0.01). In conclusion, histamine and its receptor (H1R and H2R) agonists enhance antibody production by triggering the histamine receptors (H1R and H2R), and both the H1R antagonist and the H2R antagonist positively or negatively regulate the antibody production. The findings of this study may have clinical significance.
本研究旨在描绘组胺受体（H1R 和 H2R）及其抗体产生在兔模型中的免疫调节作用。六个组，每组 18 只兔子，分别接受以下处理：载体（无菌蒸馏水，1ml/kg，bid）、组胺（100μg/kg，bid）、H1R 激动剂（HTMT，10μg/kg，bid）、H2R 激动剂（amthamine，10μg/kg，bid）、H1R 拮抗剂（pheniramine，10mg/kg，bid）或 H2R 拮抗剂（ranitidine，10mg/kg，bid）。所有动物随后用绵羊红细胞（SRBC）静脉注射免疫。在第 0 天（免疫前）、第 7、14、21、28 和 58 天（免疫后），通过 ELISA 和血凝试验（HA）测定总血清免疫球蛋白（Ig）、免疫球蛋白 M（IgM）和免疫球蛋白 G（IgG）。ELISA 和 HA 均显示出相似的 Ig、IgM 和 IgG 产生，但 ELISA 结果比 HA 更显著。结果表明，组胺可以早期（即在第 7 天）影响对 SRBC 的可检测抗体反应，这种影响持续到第 58 天。免疫调节过程显示，H1R 拮抗剂组 Ig 生成受到抑制，而 H2R 拮抗剂组 Ig 生成增强。与 H2R 激动剂组相比，H1R 激动剂组 Ig 生成增加。与 H2R 拮抗剂组相比，H1R 拮抗剂组 IgM 生成受到抑制，与 H2R 激动剂组相比，H1R 激动剂组 IgM 生成也受到抑制。与 H2R 拮抗剂组相比，H1R 拮抗剂组 IgG 生成受到抑制。相比之下，H1R 激动剂组 IgG 生成增加与 H2R 激动剂组相比。所有结果均具有统计学意义（p<0.05 或 p<0.01）。结论：组胺及其受体（H1R 和 H2R）激动剂通过触发组胺受体（H1R 和 H2R）增强抗体产生，H1R 拮抗剂和 H2R 拮抗剂均正向或负向调节抗体产生。本研究的发现可能具有临床意义。
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