Oortwijn Beatrijs D, Roos Anja, van der Boog Paul J M, Klar-Mohamad Ngaisah, van Remoortere Alexandra, Deelder André M, Daha Mohamed R, van Kooten Cees
Department of Nephrology, C3-P, Albinusdreef 2, 2333 ZA, Leiden University Medical Center, Leiden, The Netherlands.
Mol Immunol. 2007 Feb;44(5):966-73. doi: 10.1016/j.molimm.2006.03.014. Epub 2006 May 3.
IgA is found in both mucosal secretions and serum and is the dominant immunoglobulin isotype produced in humans. It exists in different molecular forms, namely monomeric IgA, dimeric IgA, polymeric IgA and secretory IgA, all exhibiting interactions with FcalphaRI/CD89 to some extent. CD89 is an activating, gamma-chain associated, Fc receptor for IgA expressed on myeloid cells. Here, we investigated the interaction of monomeric and polymeric IgA purified from human serum with CD89 using surface plasmon resonance. The results demonstrate a similar association for monomeric and polymeric IgA with CD89. In contrast, monomeric IgA dissociated more rapidly from CD89 than polymeric IgA. Removal of N-glycans from mIgA resulted is an increased association with CD89, whereas the dissociation was more rapid, resulting in binding comparable to that of untreated monomeric IgA. We conclude that the initial interaction of monomeric and polymeric IgA with CD89 is similar, whereas monomeric IgA dissociates more rapidly from CD89. In view of the large excess of monomeric IgA in serum, monomeric IgA will compete for CD89 interaction with polymeric IgA, thereby preventing cell activation initiated by receptor aggregation contributing to the anti-inflammatory role of IgA.
IgA存在于黏膜分泌物和血清中，是人类产生的主要免疫球蛋白同种型。它以不同的分子形式存在，即单体IgA、二聚体IgA、多聚体IgA和分泌型IgA，它们在一定程度上都与FcalphaRI/CD89相互作用。CD89是一种表达于髓样细胞上的、与γ链相关的、IgA的激活型Fc受体。在此，我们利用表面等离子体共振研究了从人血清中纯化的单体和多聚体IgA与CD89的相互作用。结果表明，单体和多聚体IgA与CD89的结合相似。相比之下，单体IgA比多聚体IgA从CD89上解离得更快。去除mIgA上的N-聚糖会导致其与CD89的结合增加，而解离更快，导致其结合与未处理的单体IgA相当。我们得出结论，单体和多聚体IgA与CD89的初始相互作用相似，而单体IgA从CD89上解离得更快。鉴于血清中单体IgA大量过剩，单体IgA将与多聚体IgA竞争与CD89的相互作用，从而阻止由受体聚集引发的细胞活化，这有助于IgA的抗炎作用。
