Paul S, Said S I, Thompson A B, Volle D J, Agrawal D K, Foda H, de la Rocha S
Department of Pharmacology, University of Nebraska Medical Center, Omaha 68105.
J Neuroimmunol. 1989 Jul;23(2):133-42. doi: 10.1016/0165-5728(89)90032-5.
Vasoactive intestinal peptide (VIP) is a potent relaxant of the airway smooth muscle. In this study, VIP-binding autoantibodies were observed in the plasma of 18% asthma patients and 16% healthy subjects. Immunoprecipitation studies and chromatography on DEAE-cellulose and immobilized protein G indicated that the plasma VIP-binding activity was largely due to IgG antibodies. Saturation analysis of VIP binding by the plasmas suggested the presence of one or two classes of autoantibodies, distinguished by their apparent equilibrium affinity constants (Ka). The autoantibodies from asthma patients exhibited a larger VIP-binding affinity compared to those from healthy subjects (Ka 7.8 x 10(9) M-1 and 0.13 x 10(9) M-1, respectively; P less than 0.005). The antibodies were specific for VIP, judged by their poor reaction with peptides bearing partial sequence homology with VIP (peptide histidine isoleucine, growth hormone releasing factor and secretin). IgG prepared from the plasma of an antibody-positive asthma patient inhibited the saturable binding of 125I-VIP by receptors in guinea pig lung membranes (by 39-59%; P less than 0.001). These observations are consistent with a role for the VIP autoantibodies in the airway hyperresponsiveness of asthma.
血管活性肠肽（VIP）是一种强效的气道平滑肌舒张剂。在本研究中，在18%的哮喘患者和16%的健康受试者血浆中观察到VIP结合自身抗体。免疫沉淀研究以及在DEAE - 纤维素和固定化蛋白G上的色谱分析表明，血浆VIP结合活性主要归因于IgG抗体。血浆对VIP结合的饱和分析表明存在一类或两类自身抗体，通过它们明显的平衡亲和常数（Ka）来区分。与健康受试者的自身抗体相比，哮喘患者的自身抗体表现出更大的VIP结合亲和力（Ka分别为7.8×10⁹ M⁻¹和0.13×10⁹ M⁻¹；P＜0.005）。通过它们与与VIP具有部分序列同源性的肽（肽组氨酸异亮氨酸、生长激素释放因子和促胰液素）反应较差判断，这些抗体对VIP具有特异性。从抗体阳性哮喘患者血浆中制备的IgG抑制豚鼠肺膜中受体对¹²⁵I - VIP的饱和结合（抑制39% - 59%；P＜0.001）。这些观察结果与VIP自身抗体在哮喘气道高反应性中的作用一致。
