title: Chemokine interaction with synergy-inducing molecules: fine tuning modulation of cell trafficking.
abstract: Directed migration and arrest of leukocytes during homeostasis, inflammation, and tumor development is mediated by the chemokine system, which governs leukocyte migration and activities. Although we understand well the effects of different chemokines one by one, much less was known about the potential consequences of the concomitant expression of multiple chemokines or of their interaction with inflammatory molecules on leukocyte migration and functions. In the past 10 yr, several studies revealed the existence of additional features of chemokines: they can antagonize chemokine receptors or synergize with other chemokines, also by forming heterocomplexes. Moreover, recent data show that not only chemokines but also the alarmin high-mobility group box 1 can for a complex with CXCL12, enhancing its potency on CXCR4. The molecular mechanism underlying the effect of the heterocomplex has been partially elucidated, whereas its structure is a matter of current investigations. The present review discusses the current knowledge and relevance of the functions of heterocomplexes formed between chemokines or between the chemokine CXCL12 and the alarmin high-mobility group box 1. These studies highlight the importance of taking into account, when approaching innovative therapies targeting the chemokine system, also the fact that some chemokines and molecules released in inflammation, can considerably affect the activity of chemokine receptor agonists.
authors.affiliation: Laboratory of "Chemokines in Immunity," Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland.
authors.forename: Valentina
authors.initials: V
authors.lastname: Cecchinato
authors.affiliation: Laboratory of "Chemokines in Immunity," Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland.
authors.forename: Gianluca
authors.initials: G
authors.lastname: D'Agostino
authors.affiliation: Laboratory of "Chemokines in Immunity," Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Raeli
authors.affiliation: Laboratory of "Chemokines in Immunity," Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland. mariagrazia.uguccioni@irb.usi.ch.
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Uguccioni
mesh_terms: D000818:Animals; D002465:Cell Movement; D018925:Chemokines / Q000378:metabolism*; D024243:HMGB1 Protein / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism
chemical_list: D018925:Chemokines; D024243:HMGB1 Protein; D046912:Multiprotein Complexes
keywords: CXCL12; HMGB1; cell migration; chemokine activities