Abstract
Cell adhesion molecules (CAMs) are surface ligands, usually glycoproteins, which mediate cell-to-cell adhesion. They play a critical role in maintaining tissue integrity and mediating migration of cells, and some of them also act as viral receptors. It has been known that soluble forms of the viral receptors bind to the surface glycoproteins of the viruses and neutralize them, resulting in inhibition of the viral entry into cells. Nectin-1 is one of important CAMs belonging to immunoglobulin superfamily and herpesvirus entry mediator (HVEM) is a member of the tumor necrosis factor (TNF) receptor family. Both CAMs also act as alphaherpesvirus receptor. Transgenic mice expressing the soluble form of nectin-1 or HVEM showed almost complete resistance against the alphaherpesviruses. As another CAM, sialic acid-binding immunoglobulin-like lectins (Siglecs) that recognize sialic acids are also known as an immunoglobulin superfamily member. Siglecs play an important role in the regulation of immune cell functions in infectious diseases, inflammation, neurodegeneration, autoimmune diseases and cancer. Siglec-9 is one of Siglecs and capsular polysaccharide (CPS) of group B Streptococcus (GBS) binds to Siglec-9 on neutrophils, leading to suppress host immune response and provide a survival advantage to the pathogen. In addition, Siglec-9 also binds to tumor-produced mucins such as MUC1 to lead negative immunomodulation. Transgenic mice expressing the soluble form of Siglec-9 showed significant resistance against GBS infection and remarkable suppression of MUC1 expressing tumor proliferation. This review describes recent developments in the understanding of the potency of soluble forms of CAMs in the transgenic mice and discusses potential therapeutic interventions that may alter the outcomes of certain diseases.
Highlights
IntroductionA number of cell adhesion molecules (CAMs), mediate homophilic (single type) and heterophilic (different type) cell adhesions
A number of cell adhesion molecules (CAMs), mediate homophilic and heterophilic cell adhesions
Human nectin-1 gene is mutated in cleft lip and palate/ectodermal dysplasia 1 syndrome (CLPED1), and its mutations have been associated with non-syndromic cleft lip with or without cleft palate (NSCL/P) [12]
Summary
A number of cell adhesion molecules (CAMs), mediate homophilic (single type) and heterophilic (different type) cell adhesions. Human nectin-1 gene is mutated in cleft lip and palate/ectodermal dysplasia 1 syndrome (CLPED1), and its mutations have been associated with non-syndromic cleft lip with or without cleft palate (NSCL/P) [12] This protein mediates viral entry into cells of herpes simplex viruses 1 and 2 (HSV-1, HSV-2), and pseudorabies virus (PRV) as a receptor for their glycoprotein D (gD) [13,14]. Herpesvirus entry mediator (HVEM), known as tumor necrosis factor receptor superfamily member 14 (TNFRSF14), is a cell surface receptor of the TNF-receptor superfamily. The soluble form of Siglec-9 binds to sialic acid of bacteria and tumors By using these properties, their anti-viral, bacterial and tumor potentials in transgenic mice have been shown. A brief overview of transgenic animal models expressing soluble forms of the CAMs used to evaluate their potential in the viral and bacterial infections and a tumor as well as a discussion on the possible therapeutic usage and application for disease-resistant animals will be provided
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