Anti-KC autoantibody:KC complexes cause severe lung inflammation in mice via IgG receptors
Anti-KC autoantibody:KC complexes cause severe lung inflammation in mice via IgG receptors
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DOI：
10.1165/rcmb.2006-0395oc
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发表时间：
2007-11-01
影响因子：
6.4
通讯作者：
Kurdowska, Anna K.
中科院分区：
文献类型：
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作者：
Krupa, Agnieszka;Walencka, Maria J.;Kurdowska, Anna K.
我们先前已经表明，高浓度的IL-8与抗IL-8自身抗体（抗IL-8：IL-8复合物）存在于急性呼吸窘迫综合征（ARDS）患者的肺液中，并与ARDS的发展和结局相关。我们还检测到这些复合物在ARDS患者肺组织中的沉积，但在对照组织中未检测到。此外，我们确定IgG受体（Fc γ R）介导抗IL-8：IL-8复合物的活性。在本研究中，我们在小鼠肺中产生抗KC（KC趋化因子（CXC基序）配体1（CXCL 1））自身抗体：KC免疫复合物（KC功能性IL-8），以建立自身免疫复合物诱导的肺部炎症的小鼠模型。研究了缺乏免疫复合物受体（Fc γ R）的野生型（WT）和γ链缺陷型小鼠。首先，用KC免疫小鼠以诱导抗KC自身抗体。然后，将KC经气管内给药以在肺中产生抗KC：KC复合物。抗KC：KC复合物的存在与严重肺部炎症的发生相关，然而，在γ链缺陷小鼠中，严重肺部炎症被显著抑制。其次，由于脓毒症被认为是发展为ARDS的主要危险因素，我们评估了LPS治疗的WT以及γ链缺陷小鼠的抗KC：KC复合物和肺部炎症反应的存在。我们检测了抗KC自身抗体和KC在LPS处理的小鼠肺灌洗液和组织中的复合物。此外，缺乏免疫复合物受体的γ链缺陷小鼠受到保护，免受LPS诱导的肺部炎症。我们的研究结果表明，含有自身抗体的免疫复合物有助于LPS治疗小鼠肺部炎症的发展。
We have shown previously that high concentrations of IL-8 associated with anti-IL-8 autoantibodies (anti-IL-8:IL-8 complexes) are present in lung fluids from patients with the acute respiratory distress syndrome (ARDS), and correlate both with the development and outcome of ARDS. We also detected deposition of these complexes in lung tissues from patients with ARDS but not in control tissues. Moreover, we determined that IgG receptors (Fc gamma Rs) mediate activity of anti-IL-8:IL-8 complexes. In the current study, we generated anti-KC (KC chemokine (CXC motif) ligand 1 (CXCL1)) autoantibody:KC immune complexes (KC-functional IL-8) in lungs of mice to develop a mouse model of autoimmune complex-induced lung inflammation. Both wild-type (WT) and gamma-chain-deficient mice that lack receptors for immune complexes (Fc gamma Rs) were studied. First, the mice were immunized with KC to induce anti-KC autoantibodies. Then, KC was administered intratracheally to generate anti-KC:KC complexes in the lung. Presence of anti-KC:KC complexes was associated with development of severe pulmonary inflammation that was, however, dramatically suppressed in gamma-chain-deficient mice. Second, because sepsis is considered the major risk factor for development of ARDS, we evaluated LPS-treated WT as well as,gamma-chain-deficient mice for the presence of anti-KC:KC complexes and pulmonary inflammatory responses. We detected complexes between anti-KC autoantibodies and KC in lung lavages and tissues of mice treated with LPS. Moreover, gamma-chain-deficient mice that lack receptors for immune complexes were protected from LPS-induced pulmonary inflammation. Our results suggest that immune complexes containing autoantibodies contribute to development of lung inflammation in LPS-treated mice.