Baggiolini M; Theodor-Kocher-Inst., Univ. of Bern, Switzerland.
Chemokines are major regulatory proteins of inflammation and immunity. They act mainly on leukocytes inducing migration and release responses. Chemokine activities are mediated by seven-transmembrane-domain, G-protein coupled receptors. Four CXC chemokine and five CC chemokine receptors are known (CXCR1 to 4, and CCR1 to 5). They differ in their selectivity, are differently expressed on leukocytes, and have two binding sites for chemokines. The primary receptor binding domain, for all chemokines, is a short sequence near the NH(2) terminus. Interaction at this site activates the receptor, and receptor antagonists can be obtained by truncation or substitutions within this sequence. Receptor distribution determines cellular responsiveness: the selective accumulation of certain types of leukocytes, e.g., eosinophils or T lymphocytes, can be understood, today, on the basis of selective chemokines like eotaxin, which acts on CCR3, and IP10 or Mig, which act on CXCR3. Other chemokines recognize several receptors, and are, therefore, less selective. Effects of chemokines on leukocyte progenitors, angiogenesis and tumor growth have been reported, but the data are still contradictory and the mechanisms of such growth-factor-like activities are unknown. Of considerable interest is the recent discovery that some chemokine receptors (CCR5 and CXCR4) mediate HIV-1 infection, and that chemokines as well as chemokine antagonists are inhibitory. Nearly 40 different chemokines have been isolated in the past 10 years. Most of them are chemotactic and are induced in inflammatory conditions. Some, however, are expressed constitutively and have weak if any chemotactic activity. Chemokines in search of a target? Chemokines is search of good ideas.
Keywords: AEGIS, Chemokines, Receptors, Chemokine, Chemokines, CXC, Cytokines, Eosinophils, T-Lymphocytes, Leukocytes, Protein Binding, CXC chemokine IP-10, eotaxin, AIDS
