ADAM8/MS2/CD156a: a metalloprotease-disintegrin involved in immune responses

From all ADAM family members known, interesting features of some members of this the family are is their distinct expression patterns. ADAM8 is such an example, as it was identified originally in monocytes and is expressed in many specialised cell types, among them macrophages, B-cells, granulocytes, follicle cells, glandular epithelial cells, osteoclasts, oligodendrocytes, microglia, neurons and astrocytes. ADAM8 is activated by autocatalytic prodomain removal and the substrates like the Close Homologue of L1 (CHL1) and CD23 identified so far are either involved in cell adhesion or immune responses. In turn, ADAM8 expression in some cell types such as macrophages, astrocytes and microglia is regulated by inflammatory mediators including tumor necrosis factor-α, lipopolysaccharides (LPS) and prostaglandins. Whereas embryonal development in ADAM8 deficient mice appears normal, its upregulation under inflammatory conditions like that seen in chronic neurodegeneration, after administration of LPS and in allergic asthma, seems to reflect a specific function of ADAM8 in cytokine response. From recent experiments it can be concluded that the ADAM8 induction by inflammatory cytokines serves protective functions, e.g. by shedding of receptors mediating inflammatory responses or by degrading immune mediators directly.