Ueda T, Rieu P, Brayer J, Arnaout M A
Department of Medicine, Massachusetts General Hospital, Boston 02129.
Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10680-4. doi: 10.1073/pnas.91.22.10680.
The divalent cation-dependent interaction of the beta 2 integrin CR3 (CD11b/CD18) with the major complement opsonic C3 fragment iC3b is an important component of the central role of CR3 in inflammation and immune clearance. In this investigation we have identified the iC3b binding site in CR3. A recombinant fragment representing the CR3 A-domain, a 200-amino acid region in the ectodomain of the CD11b subunit, bound to iC3b directly and in a divalent cation-dependent manner. The iC3b binding site was further localized to a short linear peptide that also bound iC3b directly and inhibited iC3b binding to the A-domain as well as to CR3 expressed by human neutrophils. These data establish a major recognition function for the integrin A-domain and have important implications for development of novel antiinflammatory therapeutics.
β2整合素CR3（CD11b/CD18）与主要补体调理素C3片段iC3b之间的二价阳离子依赖性相互作用，是CR3在炎症和免疫清除中核心作用的重要组成部分。在本研究中，我们确定了CR3中的iC3b结合位点。一个代表CR3 A结构域的重组片段，即CD11b亚基胞外域中的一个200个氨基酸的区域，以二价阳离子依赖性方式直接与iC3b结合。iC3b结合位点进一步定位于一个短线性肽，该肽也直接结合iC3b，并抑制iC3b与A结构域以及人中性粒细胞表达的CR3的结合。这些数据确立了整合素A结构域的主要识别功能，并对新型抗炎治疗药物的开发具有重要意义。
