Immunology Department, Federal State Budgetary Scientific Institution «Institute of Experimental Medicine», Saint Petersburg, Russia.
Virology Department, Federal State Budgetary Scientific Institution «Institute of Experimental Medicine», Saint Petersburg, Russia.
Front Immunol. 2021 Jul 14;12:689436. doi: 10.3389/fimmu.2021.689436. eCollection 2021.
We investigated the reaction of mouse peritoneal mast cells (MCs) after IgG-containing immune complex introduction using A/H5N1 and A/H1N1pdm09 influenza viruses as antigens. The sera of immune mice served as a source of IgG antibodies. The concentration of histamine in the supernatants was determined at 4 hours after incubation with antisera and virus. We compared the contribution of MCs to the pathogenesis of post-immunization influenza infection with A/H5N1 and A/H1N1 influenza viruses in mice. The mice were immunized parenterally with inactivated viruses and challenged with lethal doses of drift A/H5N1 and A/H1N1 influenza viruses on the 14 day after immunization. Simultaneously, half of the mice were injected intraperitoneally with a mixture of histamine receptor blockers (chloropyramine and quamatel). In experiments, the immune complex formed by A/H5N1 virus and antiserum caused a significant increase in the histamine release compared to immune serum or the virus alone. With regard to the A/H1N1 virus, such an increase was not significant. A/H1N1 immunization caused detectable HI response in mice at 12 day after immunization, in contrast to the A/H5N1 virus. After challenge of A/H5N1-immunized mice, administration of antihistamines increased the survival rate by up to 90%. When infecting the A/H1N1-immunized mice, 90% of the animals were already protected from lethal infection by day 14; the administration of histamine receptor blockers did not increase survival. Histological examination of the lungs has shown that toluidine blue staining allows to estimate the degree of MC degranulation. The possibility of activation of murine MCs by IgG-containing immune complexes has been shown. In a model of influenza infection, it was shown that the administration of histamine receptor blockers increased survival. When the protection was formed faster due to the earlier production of HI antibodies, the administration of histamine receptor blockers did not significantly affect the course of the infection. These data allow to propose that even if there are antibody-dependent MC reactions, they can be easily stopped by the administration of histamine receptor blockers.
我们研究了用 A/H5N1 和 A/H1N1pdm09 流感病毒作为抗原引入含 IgG 免疫复合物后小鼠腹腔肥大细胞 (MC)的反应。免疫小鼠的血清作为 IgG 抗体的来源。在与抗血清和病毒孵育 4 小时后，测定上清液中组胺的浓度。我们比较了 MC 对免疫后感染 A/H5N1 和 A/H1N1 流感病毒的致病性的贡献。用灭活病毒对小鼠进行肌内免疫，并在免疫后第 14 天用漂移 A/H5N1 和 A/H1N1 流感病毒的致死剂量对其进行攻毒。同时，一半的小鼠腹腔内注射组胺受体阻滞剂（氯苯那敏和羟嗪）混合物。在实验中，与单独的免疫血清或病毒相比，A/H5N1 病毒和抗血清形成的免疫复合物导致组胺释放显著增加。对于 A/H1N1 病毒，这种增加并不显著。与 A/H1N1 病毒相比，A/H1N1 免疫在免疫后 12 天在小鼠中引起可检测的 HI 反应。用 A/H5N1 免疫的小鼠攻毒后，给予抗组胺药可将存活率提高到 90%。感染 A/H1N1 免疫的小鼠时，到第 14 天，90%的动物已免受致死性感染的保护；组胺受体阻滞剂的给药并未增加存活率。对肺组织的组织学检查表明，甲苯胺蓝染色可用于估计 MC 脱颗粒的程度。已经显示 IgG 包含的免疫复合物可以激活鼠 MC。在流感感染模型中，显示组胺受体阻滞剂的给药增加了存活率。当由于更早产生 HI 抗体而更快地形成保护时，组胺受体阻滞剂的给药对感染过程没有显著影响。这些数据表明，即使存在抗体依赖性 MC 反应，也可以通过给予组胺受体阻滞剂轻松阻止。
