title: Neutrophils produce biologically active macrophage inflammatory protein-3alpha (MIP-3alpha)/CCL20 and MIP-3beta/CCL19.
abstract: Macrophage inflammatory protein-3alpha (MIP-3alpha)/CCL20 and MIP-3beta/CCL19 are members of the CC chemokine subfamily which exert their effects through specific receptors, CCR6 and CCR7, respectively. Previously, we have reported that human neutrophils have the capacity to produce a number of chemokines, including IL-8/CXCL8, GROalpha/CXCL1, IP-10/CXCL10, and MIG/CXCL9. Herein, we show that neutrophils also have the ability to express and release MIP-3alpha/CCL20 and MIP-3beta/CCL19 when cultured with either LPS or TNF-alpha. We also report that MIP-3alpha/CCL20 and MIP-3beta/CCL19 production by LPS-stimulated neutrophils is negatively modulated by IL-10. Remarkably, we found that supernatants harvested from stimulated neutrophils not only induced chemotaxis of both immature and mature dendritic cells (DC), but also triggered rapid integrin-dependent adhesion of CCR6- and CCR7-expressing lymphocytes to purified VCAM-1 and ICAM-1, respectively. Importantly, both chemotaxis and rapid integrin-dependent adhesion were dramatically suppressed by anti-MIP-3alpha/CCL20 and anti-MIP-3beta/CCL19 neutralizing antibodies, indicating that MIP-3alpha/CCL20 and MIP-3beta/CCL19 present in the supernatants were both biologically active. As these chemokines are primarily chemotactic for DC and specific lymphocyte subsets, the ability of neutrophils to produce MIP-3alpha/CCL20 and MIP-3beta/CCL19 might be significant in orchestrating the recruitment of these cell types to the inflamed sites and therefore in contributing to the regulation of the immune response.
authors.affiliation: Department of Pathology, Section of General Pathology, University of Verona, Verona, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Scapini
authors.forename: C
authors.initials: C
authors.lastname: Laudanna
authors.forename: C
authors.initials: C
authors.lastname: Pinardi
authors.forename: P
authors.initials: P
authors.lastname: Allavena
authors.forename: A
authors.initials: A
authors.lastname: Mantovani
authors.forename: S
authors.initials: S
authors.lastname: Sozzani
authors.forename: M A
authors.initials: MA
authors.lastname: Cassatella
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D002478:Cells, Cultured; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics; D002633:Chemotaxis; D017077:Culture Media, Conditioned; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
chemical_list: C515460:CCL19 protein, human; C108355:CCL20 protein, human; C106311:CCR6 protein, human; C515461:Ccl19 protein, mouse; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D019742:Chemokines, CC; D017077:Culture Media, Conditioned; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1