ICAM-1: Isoforms and Phenotypes

Abstract

Intercellular adhesion molecule-1 (ICAM-1) plays an important role in leukocyte trafficking, immunological synapse formation and, numerous cellular immune responses. Although considered a single glycoprotein, there are multiple membrane bound and soluble ICAM-1 isoforms which arise from alternative splicing and proteolytic cleavage during inflammatory responses. The function and expression of these isoforms on various cell types is poorly understood. In the generation of ICAM-1-deficient mice, two isoform-deficient ICAM-1 mutants were inadvertently produced due to alternative splicing. These mice along with true ICAM-1-deficient mice and newly generated ICAM-1 transgenic mice have provided the opportunity to begin examining the role of ICAM-1 isoforms (singly or in combination) in various disease settings. In this review we highlight the sharply contrasting disease phenotypes using ICAM-1 isoform mutant mice. These studies demonstrate that ICAM-1 immunobiology is highly complex but that individual isoforms, aside from the full-length molecule, make significant contributions to disease development and pathogenesis.

Functional–morphological parameters, aqueous flare and cytokines in macular oedema with branch retinal vein occlusion after ranibizumab

“…On the other hand, multiple linear regression analysis revealed that both IL-8 and sICAM-1 were strongly correlated with the aqueous flare value at the 1st recurrence. ICAM-1 is a transmembrane molecule and is an important member of the immunoglobulin superfamily of proteins that participates in many processes such as leucocyte endothelial transmigration 16. Upregulation of ICAM-1 expression leads to an increase in rolling and adhesion of leucocytes to vein walls 16.…”

“…ICAM-1 is a transmembrane molecule and is an important member of the immunoglobulin superfamily of proteins that participates in many processes such as leucocyte endothelial transmigration 16. Upregulation of ICAM-1 expression leads to an increase in rolling and adhesion of leucocytes to vein walls 16. In patients with retinal vein occlusion, it has been reported that leucocytes show increased rolling and adhesion leading to stagnation of blood flow 17.…”

ICAM-1–expressing neutrophils exhibit enhanced effector functions in murine models of endotoxemia

“…[1][2][3] It is a key adhesion molecule with significant signaling properties that has been associated with numerous cellular responses such as cell adhesion, migration, and aggregation. [4][5][6] ICAM-1 is constitutively expressed on the surface of a wide range of cells, including endothelial and epithelial cells, smooth muscle cells, pericytes, fibroblasts, and keratinocytes.…”

Membrane-bound ICAM-1 contributes to the onset of proinvasive tumor stroma by controlling acto-myosin contractility in carcinoma-associated fibroblasts

“…ICAM-1 is considered to be an inflammatory responsive gene, whose expression is highly induced in injured tissues [17, 18]. The membrane-bound ICAM-1 isoform is expressed at the cell surface of a variety of cell types including endothelial, epithelial, immune cells and fibroblasts [19–21], but it can also be found as a soluble secreted form (sICAM-1) [22–24].…”