ICAM1

ICAM-1, or intercellular adhesion molecule 1, also known as CD54, is a member of the immunoglobulin superfamily of cell surface proteins. It is a type I transmembrane glycoprotein typically around 90–110 kDa when glycosylated. The protein consists of an N-terminal signal sequence, five extracellular immunoglobulin-like domains, a single transmembrane helix, and a short cytoplasmic tail. A soluble form, sICAM-1, is generated by proteolytic shedding of the ectodomain and can be detected in body fluids.

ICAM-1 is constitutively expressed on vascular endothelial cells and various leukocytes; expression on other cell types occurs under certain conditions. Its surface levels are upregulated by inflammatory cytokines such as interleukin-1, tumor necrosis factor-alpha, and interferon-gamma, often via NF-κB signaling. This upregulation facilitates leukocyte recruitment to sites of inflammation.

ICAM-1 mediates adhesion of leukocytes to the endothelium and their diapedesis during immune surveillance and inflammatory responses. It binds to integrins LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) on leukocytes, supporting firm adhesion and transmigration. In addition to immune roles, ICAM-1 serves as a receptor for certain pathogens, most notably rhinoviruses, enabling viral entry into host cells. It may also contribute to cell–cell interactions in other tissues and contexts.

Soluble ICAM-1 levels rise in various inflammatory and infectious conditions and are used as a biomarker in some settings. Reduced or aberrant ICAM-1–mediated adhesion can affect immune cell trafficking, while excessive ICAM-1–mediated adhesion has been implicated in vascular injury, atherosclerosis, and tumor metastasis. ICAM-1 has been explored as a therapeutic target to modulate inflammatory responses, though clinical success remains limited.