Altieri D C
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
J Immunol. 1991 Sep 15;147(6):1891-8.
The group of leukocyte integrins CD11a-c/CD18 coordinate disparate adhesion reactions in the immune system through a regulated process of ligand recognition. The participation of the receptor divalent ion binding site(s) in this mechanism of ligand binding has been investigated. As compared with other divalent cations, Mn2+ ions have the unique property to dramatically stimulate the adhesive functions of the leukocyte integrin CD11b/CD18 (Mac-1), expressed on myelo-monocytic cells. This is reflected in a three- to fivefold increased early monocyte adhesion (less than 20 min) to resting, unperturbed endothelial cells, and increased association of CD11b/CD18 with its soluble ligands fibrinogen and factor X. CD11b/CD18 ligand recognition in the presence of Mn2+ ions is specific, time and concentration dependent, and inhibited by anti-CD11b mAb. At variance with Ca(2+)-containing reactions where CD11b/CD18 functions as an inducible receptor activated by adenine nucleotides or chemoattractants, Mn2+ ions induce per se a constitutive maximal ligand binding capacity of CD11b/CD18, that is not further modulated by cell stimulation. Rather than quantitative changes in surface density, Mn2+ ions increase the affinity of CD11b/CD18 for its complementary ligands up to 10-fold, as judged by Scatchard plot analysis of receptor:ligand interaction under these conditions. Furthermore, monocyte exposure to Mn2+ ions induces the expression of activation-dependent neo-antigenic epitopes on CD11b/CD18, selectively recognized by mAb 7E3. These data suggest that in addition to cell-activating stimuli, favorable engagement of divalent ion binding site(s) can provide an alternative pathway to rapidly regulate the receptor affinity of leukocyte integrins.
白细胞整合素CD11a - c/CD18通过配体识别的调控过程协调免疫系统中不同的黏附反应。已对受体二价离子结合位点在这种配体结合机制中的参与情况进行了研究。与其他二价阳离子相比，Mn2 +离子具有独特的性质，能显著刺激髓单核细胞上表达的白细胞整合素CD11b/CD18（Mac - 1）的黏附功能。这表现为早期单核细胞（少于20分钟）与静息、未受干扰的内皮细胞的黏附增加三到五倍，以及CD11b/CD18与其可溶性配体纤维蛋白原和因子X的结合增加。在Mn2 +离子存在下，CD11b/CD18的配体识别具有特异性、时间和浓度依赖性，并受到抗CD11b单克隆抗体的抑制。与含Ca(2 +)的反应不同，在含Ca(2 +)的反应中CD11b/CD18作为由腺嘌呤核苷酸或趋化因子激活的诱导性受体起作用，而Mn2 +离子本身诱导CDI1b/CD18具有组成性的最大配体结合能力，细胞刺激不会进一步对其进行调节。通过在这些条件下对受体 - 配体相互作用进行Scatchard作图分析判断，Mn2 +离子不是增加表面密度的定量变化，而是使CD11b/CD18对其互补配体的亲和力增加高达10倍。此外单核细胞暴露于Mn2 +离子会诱导CD11b/CD18上激活依赖性新抗原表位的表达，该表位可被单克隆抗体7E3选择性识别。这些数据表明，除了细胞激活刺激外，二价离子结合位点的良好结合可以提供一条快速调节白细胞整合素受体亲和力的替代途径。
