Terry R W, Kwee L, Levine J F, Labow M A
Molecular Sciences Group, Hoffmann-La Roche Inc., Nutley, NJ 07110-1199.
Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):5919-23. doi: 10.1073/pnas.90.13.5919.
VCAM-1 is an immunoglobulin superfamily member that mediates adhesion of a variety of leukocytes to endothelial cells. VCAM expression has been associated with a variety of disease states and has been implicated in a number of normal processes. The predominant form of VCAM produced in human endothelial cells is a transmembrane protein containing seven immunoglobulin domains. In this study the murine VCAM gene has been characterized to allow the function(s) of VCAM to be studied in a small genetically accessible animal. While expression of an mRNA encoding a seven-immunoglobulin-domain transmembrane VCAM protein was seen in most tissues, the predominant change in VCAM expression upon interleukin 1 beta treatment was the induction of an alternatively spliced VCAM mRNA containing only the first three immunoglobulin domains. This message encodes a glycosylphosphatidylinositol (GPI)-anchored form of VCAM, VCAMGPI. VCAMGPI was efficiently cleaved from the cell surface by phosphatidylinositol-specific phospholipase C, mediated adhesion to leukocytes in a very late antigen 4-dependent manner, and was produced by mouse endothelial cell lines in culture. These data demonstrate that alternate forms of VCAM are produced under different physiological conditions and suggest that VCAMGPI may have a distinct role in inflammatory processes.
血管细胞黏附分子-1（VCAM-1）是免疫球蛋白超家族成员，介导多种白细胞与内皮细胞的黏附。VCAM的表达与多种疾病状态相关，并参与许多正常生理过程。人内皮细胞产生的VCAM的主要形式是一种含有七个免疫球蛋白结构域的跨膜蛋白。在本研究中，已对小鼠VCAM基因进行了表征，以便在一种易于进行基因操作的小型动物中研究VCAM的功能。虽然在大多数组织中都能看到编码含七个免疫球蛋白结构域的跨膜VCAM蛋白的mRNA的表达，但白细胞介素1β处理后VCAM表达的主要变化是诱导产生一种只含前三个免疫球蛋白结构域的可变剪接的VCAM mRNA。这条信息编码一种糖基磷脂酰肌醇（GPI）锚定形式的VCAM，即VCAMGPI。VCAMGPI能被磷脂酰肌醇特异性磷脂酶C从细胞表面有效切割下来，以一种非常晚期抗原4依赖的方式介导与白细胞的黏附，并且由培养中的小鼠内皮细胞系产生。这些数据表明，在不同生理条件下会产生VCAM的不同形式，并提示VCAMGPI在炎症过程中可能具有独特作用。
