Gosset P, Tillie-Leblond I, Oudin S, Parmentier O, Wallaert B, Joseph M, Tonnel A B
Unité INSERM U416, Institut Pasteur, Lille, France.
J Allergy Clin Immunol. 1999 Feb;103(2 Pt 1):289-97. doi: 10.1016/s0091-6749(99)70504-x.
The alveolar macrophage (AM) expresses the low affinity IgE receptor and has the ability to produce not only several proinflammatory cytokines (TNF-alpha, IL-1, IL-6) but also antiinflammatory cytokines (IL-1 receptor antagonist [IL-lra], IL-10), chemokines (IL-8, monocyte chemotactic protein-1 [MCP-1]), and macrophage inflammatory protein-1alpha (MIP-1alpha).
The aim of this study was to evaluate the capacity of the AM from patients with allergic asthma and control subjects to produce chemokines and antiinflammatory versus proinflammatory cytokines after activation by IgE receptors and to define the role of CD23 in this activation.
AMs were collected by bronchoalveolar lavage from 13 patients with allergic asthma and 14 healthy subjects. Adherent AMs were activated either by the successive addition of IgE and anti-IgE or by monoclonal mouse IgG anti-CD23 or by a control monoclonal mouse antibody. TNF, IL-1beta, IL-1ra, IL-10, IL-8, MCP-1, and MIP-1alpha levels were evaluated in supernatants of AMs incubated for 18 hours and in some cases after 4 hours of incubation.
Activation by IgE and anti-IgE antibodies significantly increased the production of TNF, IL-1beta, IL-8, MCP-1, MIP-lalpha, and IL-10 in both control subjects and patients with asthma, whereas the increase for IL-1ra was only significant for the control subjects. Whereas F(ab) fragments of anti-CD23 antibodies inhibited IgE plus anti-IgE-induced cytokine production, activation by monoclonal IgG anti-CD23 antibodies reproduced the effect of IgE immune complexes. At 4 hours, the secretion of proinflammatory cytokines was increased by activation by IgE receptors, in contrast to antiinflammatory cytokines. In addition, analysis of the balance between proinflammatory and antiinflammatory cytokines showed that IgE-dependent activation largely favored the proinflammatory cytokines, particularly in patients with asthma.
IgE-dependent activation by the FcepsilonRII receptor upregulates the synthesis of both chemokines and antiinflammatory cytokines in addition to proinflammatory cytokines. However, AMs from patients with allergic asthma may promote airway inflammation after activation by IgE receptors through its preferential effect on proinflammatory cytokines.
肺泡巨噬细胞（AM）表达低亲和力IgE受体，不仅能够产生多种促炎细胞因子（肿瘤坏死因子-α、白细胞介素-1、白细胞介素-6），还能产生抗炎细胞因子（白细胞介素-1受体拮抗剂[IL-1ra]、白细胞介素-10）、趋化因子（白细胞介素-8、单核细胞趋化蛋白-1[MCP-1]）以及巨噬细胞炎性蛋白-1α（MIP-1α）。
本研究旨在评估过敏性哮喘患者和对照受试者的肺泡巨噬细胞在被IgE受体激活后产生趋化因子以及抗炎与促炎细胞因子的能力，并确定CD23在这种激活过程中的作用。
通过支气管肺泡灌洗从13例过敏性哮喘患者和14名健康受试者中收集肺泡巨噬细胞。贴壁的肺泡巨噬细胞通过依次添加IgE和抗IgE、单克隆小鼠IgG抗CD23或对照单克隆小鼠抗体进行激活。在孵育18小时的肺泡巨噬细胞上清液中以及在某些情况下孵育4小时后评估肿瘤坏死因子、白细胞介素-1β、白细胞介素-1ra、白细胞介素-10、白细胞介素-8、MCP-1和MIP-1α水平。
IgE和抗IgE抗体激活显著增加了对照受试者和哮喘患者中肿瘤坏死因子、白细胞介素-1β、白细胞介素-8、MCP-1、MIP-1α和白细胞介素-10的产生，而白细胞介素-1ra的增加仅在对照受试者中显著。抗CD23抗体的F(ab)片段抑制了IgE加抗IgE诱导的细胞因子产生，单克隆IgG抗CD23抗体激活再现了IgE免疫复合物的作用。在4小时时，与抗炎细胞因子相反，IgE受体激活增加了促炎细胞因子的分泌。此外，促炎和抗炎细胞因子之间平衡的分析表明，IgE依赖性激活在很大程度上有利于促炎细胞因子，尤其是在哮喘患者中。
FcepsilonRII受体的IgE依赖性激活除了上调促炎细胞因子外，还上调趋化因子和抗炎细胞因子的合成。然而，过敏性哮喘患者的肺泡巨噬细胞在被IgE受体激活后可能通过其对促炎细胞因子的优先作用促进气道炎症。
