Diamond M S, Staunton D E, Marlin S D, Springer T A
Committee on Cell & Developmental Biology, Harvard Medical School, Boston, Massachusetts 02115.
Cell. 1991 Jun 14;65(6):961-71. doi: 10.1016/0092-8674(91)90548-d.
Both the integrins LFA-1 and Mac-1 bind to ICAM-1, an immunoglobulin superfamily member. Previously, we localized the binding sites of LFA-1 and the major group of human rhinoviruses to the first NH2-terminal immunoglobulin-like domain of ICAM-1. Here, we show that the binding site on ICAM-1 for Mac-1 is unexpectedly distinct from that for LFA-1 and maps to the third NH2-terminal immunoglobulin-like domain. These findings provide a function for the tandem duplication of immunoglobulin-like domains in ICAM-1 and have implications for other immunoglobulin superfamily members. Mutations at two sites in the third domain that destroy consensus sequences for N-linked glycosylation enhance binding to purified Mac-1. Agents that interfere with carbohydrate processing provide evidence that the size of the N-linked oligosaccharide side chains on ICAM-1 affects binding to Mac-1 but not to LFA-1. Thus, we suggest that the extent of glycosylation on ICAM-1 may regulate adhesion to LFA-1 or Mac-1 in vivo.
整合素淋巴细胞功能相关抗原-1（LFA-1）和巨噬细胞抗原-1（Mac-1）都能与细胞间黏附分子-1（ICAM-1，一种免疫球蛋白超家族成员）结合。此前，我们已将LFA-1和主要种类的人鼻病毒的结合位点定位到ICAM-1的第一个氨基末端免疫球蛋白样结构域。在此，我们表明ICAM-1上Mac-1的结合位点出人意料地不同于LFA-1的结合位点，且定位于第三个氨基末端免疫球蛋白样结构域。这些发现为ICAM-1中免疫球蛋白样结构域的串联重复提供了一种功能，并对其他免疫球蛋白超家族成员具有启示意义。第三个结构域中破坏N-连接糖基化共有序列的两个位点的突变增强了与纯化的Mac-1的结合。干扰碳水化合物加工的试剂提供了证据，表明ICAM-1上N-连接寡糖侧链的大小影响与Mac-1的结合，但不影响与LFA-1的结合。因此，我们认为ICAM-1上的糖基化程度可能在体内调节与LFA-1或Mac-1的黏附。
