title: Synergy-inducing chemokines enhance CCR2 ligand activities on monocytes.
abstract: The migration of monocytes to sites of inflammation is largely determined by their response to chemokines. Although the chemokine specificities and expression patterns of chemokine receptors are well defined, it is still a matter of debate how cells integrate the messages provided by different chemokines that are concomitantly produced in physiological or pathological situations in vivo. We present evidence for one regulatory mechanism of human monocyte trafficking. Monocytes can integrate stimuli provided by inflammatory chemokines in the presence of homeostatic chemokines. In particular, migration and cell responses could occur at much lower concentrations of the CCR2 agonists, in the presence of chemokines (CCL19 and CCL21) that per se do not act on monocytes. Binding studies on CCR2(+) cells showed that CCL19 and CCL21 do not compete with the CCR2 agonist CCL2. Furthermore, the presence of CCL19 or CCL21 could influence the degradation of CCL2 and CCL7 on cells expressing the decoy receptor D6. These findings disclose a new scenario to further comprehend the complexity of chemokine-based monocyte trafficking in a vast variety of human inflammatory disorders.
authors.affiliation: Institute for Research in Biomedicine, Bellinzona, Switzerland.
authors.forename: Katrin
authors.initials: K
authors.lastname: Kuscher
authors.forename: Gabriela
authors.initials: G
authors.lastname: Danelon
authors.forename: Samantha
authors.initials: S
authors.lastname: Paoletti
authors.forename: Luisa
authors.initials: L
authors.lastname: Stefano
authors.forename: Milena
authors.initials: M
authors.lastname: Schiraldi
authors.forename: Vibor
authors.initials: V
authors.lastname: Petkovic
authors.forename: Massimo
authors.initials: M
authors.lastname: Locati
authors.forename: Basil O
authors.initials: BO
authors.lastname: Gerber
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Uguccioni
mesh_terms: D000595:Amino Acid Sequence; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D054415:Chemokine CCL19 / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D018932:Chemokine CCL2 / Q000276:immunology / Q000494:pharmacology; D054421:Chemokine CCL21 / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D054410:Chemokine CCL7 / Q000276:immunology / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology / Q000378:metabolism; D006025:Glycosaminoglycans / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D010766:Phosphorylation / Q000276:immunology; D017434:Protein Structure, Tertiary; D054447:Receptors, CCR10 / Q000276:immunology / Q000378:metabolism; D054390:Receptors, CCR2 / Q000819:agonists / Q000737:chemistry / Q000276:immunology*; D054400:Receptors, CCR7 / Q000819:agonists / Q000737:chemistry / Q000276:immunology*; D000097628:Chemokine Receptor D6
chemical_list: D054415:Chemokine CCL19; D018932:Chemokine CCL2; D054421:Chemokine CCL21; D054410:Chemokine CCL7; D048049:Extracellular Signal-Regulated MAP Kinases; D006025:Glycosaminoglycans; D008024:Ligands; D054447:Receptors, CCR10; D054390:Receptors, CCR2; D054400:Receptors, CCR7; D000097628:Chemokine Receptor D6; C515334:CCR2 protein, human; C515370:CCR7 protein, human