title: CXCL9 and 11 in patients with pulmonary sarcoidosis: a role of alveolar macrophages.
abstract: Interferon-inducible protein-10 (IP-10)/CXCL10, which is a ligand for CXC chemokine receptor 3 (CXCR3), is known to be involved in the pathogenesis of pulmonary sarcoidosis. However, the roles of monokine induced by interferon gamma (Mig)/CXCL9 and interferon-inducible T cell alpha chemoattractant (I-TAC)/CXCL11, which are also CXCR3 ligands, remain unclear. Mig/CXCL9, IP-10/CXCL10 and I-TAC/CXCL11 in both bronchoalveolar lavage fluid (BALF) and serum in patients with pulmonary sarcoidosis were measured by enzyme-linked immunosorbent assay (ELISA). The expression of these chemokines in alveolar macrophages was examined using ELISA, quantitative real-time polymerase chain reaction and immunostaining. In BALF, Mig/CXCL9 and IP-10/CXCL10 were significantly elevated in stage II sarcoidosis as compared with the levels in healthy volunteers. In serum, Mig/CXCL9 and I-TAC/CXCL11 were increased in stage II of the disease. The levels of all CXCR3 ligands in BALF were correlated with the numbers of both total and CD4(+) lymphocytes. Alveolar macrophages were stained positive for all CXCR3 ligands and produced increased amounts of these chemokines. Positive staining of the three chemokines was also observed in the epithelioid and giant cells in the sarcoid lungs. These findings suggest that Mig/CXCL9 and I-TAC/CXCL11 as well as IP-10/CXCL10 play important roles in the accumulation of Th1 lymphocytes in sarcoid lungs.
authors.affiliation: Department of Internal Medicine and Molecular Therapeutics, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan. yasuhiko@clin.med.tokushima-u.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Nishioka
authors.forename: K
authors.initials: K
authors.lastname: Manabe
authors.forename: J
authors.initials: J
authors.lastname: Kishi
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Inayama
authors.forename: M
authors.initials: M
authors.lastname: Azuma
authors.forename: S
authors.initials: S
authors.lastname: Sone
mesh_terms: D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D008024:Ligands; D008168:Lung / Q000276:immunology; D018655:Lymphocyte Count; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D017565:Sarcoidosis, Pulmonary / Q000276:immunology*; D012720:Severity of Illness Index
chemical_list: C114753:CXCL10 protein, human; C515202:CXCL11 protein, human; C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D008024:Ligands