HUMAN CHEMOKINES - AN UPDATE

Interleukin 8, the first chemokine to be characterized, was discovered nearly ten years ago. Today, more than 30 human chemokines are known. They are often upregulated in inflammation and act mainly on leukocyt es inducing migration and release responses. The present review deals largely with the new developments of the last three years. Several str uctural studies have shown that most chemokines form dimers. The dimer s, however, dissociate upon dilution, and the monomers constitute the biologically active form. Chemokine activities are mediated by seven-t ransmembrane-domain, G protein coupled receptors, five of which were d iscovered in the past three years. The primary receptor-binding domain of all chemokines is near the NH2 terminus, and antagonists can be ob tained by truncation or substitutions in this region. Major progress h as been made in the understanding of chemokine actions on T lymphocyte s that respond to several CC chemokines but also to IP10 and Mig, two CXC chemokines that selectively attract T cells via a novel receptor. Effects of chemokines on angiogenesis and tumor growth have been repor ted, but the data are still contradictory and the mechanisms unknown. Of considerable interest is the recent discovery that some chemokines function as HIV-suppressive factors by interacting with chemokine rece ptors which, together with CD4, were recognized as the binding sites f or HIV-1.