title: CXCR3 ligands are augmented during the pathogenesis of pulmonary sarcoidosis.
abstract: We and other investigators have hypothesised that the CXC chemokine receptor (CXCR)3/CXCR3 ligand biological axis is involved in the formation of sarcoid lung granulomas; however, significant discrepancies in the current literature remain. In an effort to clarify previous conflicting findings, we performed the largest observational study to date of interferon-inducible ELR(-) (lacking the sequence glutamic acid-leucine-arginine) CXC chemokines in sarcoid bronchoalveolar fluid (BALF). BALF chemokine levels from sarcoid patients (n = 72) and healthy controls (n = 8) were measured with the ELISA method. Immunohistochemical staining was performed for CXCR3 and its ligands. BALF CXC chemokine ligand (CXCL)10 levels from sarcoid patients were not significantly increased compared with controls. BALF CXCL11 levels from sarcoid patients demonstrated a trend towards elevation; subgroup analysis by stage showed significant BALF CXCL11 elevation in stage I sarcoid patients compared with controls. BALF CXCL9 levels were elevated from sarcoid patients compared with controls. CXC11, CXCL9 and CXCR3 were expressed from epithelioid histiocytes, multinucleated giant cells and other inflammatory cells forming sarcoid lung granulomas. Our data suggest that CXCL9 and CXCL11 are important mediators in recruiting CXCR3-expressing cells. Importantly, we have made the novel observation that both lymphocytes and cells of monocyte linage express CXCR3 and are involved in the formation of sarcoid lung granulomas.
authors.affiliation: Dept of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1786, USA.
authors.forename: A
authors.initials: A
authors.lastname: Busuttil
authors.forename: S S
authors.initials: SS
authors.lastname: Weigt
authors.forename: M P
authors.initials: MP
authors.lastname: Keane
authors.forename: Y Y
authors.initials: YY
authors.lastname: Xue
authors.forename: V
authors.initials: V
authors.lastname: Palchevskiy
authors.forename: M D
authors.initials: MD
authors.lastname: Burdick
authors.forename: C
authors.initials: C
authors.lastname: Huang
authors.forename: D A
authors.initials: DA
authors.lastname: Zisman
authors.forename: M
authors.initials: M
authors.lastname: Fishbein
authors.forename: J P
authors.initials: JP
authors.lastname: Lynch
authors.forename: R M
authors.initials: RM
authors.lastname: Strieter
authors.forename: R M
authors.initials: RM
authors.lastname: Elashoff
authors.forename: J A
authors.initials: JA
authors.lastname: Belperio
mesh_terms: D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016022:Case-Control Studies; D019743:Chemokines, CXC / Q000378:metabolism*; D005260:Female; D006801:Humans; D007372:Interferons / Q000502:physiology; D008024:Ligands; D008297:Male; D008875:Middle Aged; D054367:Receptors, CXCR3 / Q000378:metabolism*; D017565:Sarcoidosis, Pulmonary / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D012720:Severity of Illness Index
chemical_list: C515187:CXCR3 protein, human; D019743:Chemokines, CXC; D008024:Ligands; D054367:Receptors, CXCR3; D007372:Interferons