title: Neutrophil chemotaxis in granulomatosis with polyangiitis (Wegener's) and idiopathic pulmonary fibrosis.
abstract: The presence of antineutrophil cytoplasmic antibodies in granulomatosis with polyangiitis (Wegener's) (GPA) implicates the neutrophil as a key effector cell. Previous studies have reported elevated neutrophil counts in the lung, although the determinants of neutrophil chemotaxis in the GPA lung are unknown. Bronchoalveolar lavage fluid (BALF) cell counts, myeloperoxidase (MPO) and chemokines were measured in 27 patients with GPA, 20 disease controls with idiopathic pulmonary fibrosis (IPF) and six healthy controls. CXC chemokine ligand (CXCL)8, interleukin (IL)-1β, epithelial neutrophil-activating protein 78, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor were measured by ELISA. The neutrophil chemotactic potential of BALF was investigated using the under-agarose method, and specific antibodies were used to examine the role of CXCL8 and IL-1β. GPA BALF had an increased neutrophil percentage, and elevated MPO, CXCL8 and G-CSF concentrations compared with healthy controls. Chemotaxis of control neutrophils towards BALF from patients with active (p=0.006) and remission (p=0.077) GPA, and IPF (p=0.001) patients was increased compared with normal controls. BALF-induced chemotaxis correlated with BALF IL-1β (r=0.761, p=0.001) and CXCL8 (r=0.640, p=0.012) in GPA, and was inhibited by anti-CXCL8 (85%; p<0.001) and anti-IL-1β (69%; p<0.001). Our study confirms a neutrophilia and pro-inflammatory alveolar milieu that persists in clinical remission. CXCL8 and IL-1β appear to play important roles in the neutrophil chemotactic response to BALF.
authors: Lung Injury and Fibrosis Treatment Programme, Dept of Medical Sciences, University ofBirmingham, Birmingham, UK.
authors: A G
authors: AG
authors: Richter
authors: G D
authors: GD
authors: Perkins
authors: A
authors: A
authors: Chavda
authors: E
authors: E
authors: Sapey
authors: L
authors: L
authors: Harper
authors: D R
authors: DR
authors: Thickett
mesh_terms: D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D054365:Chemokine CXCL5 / Q000032:analysis; D002634:Chemotaxis, Leukocyte; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000032:analysis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis; D014890:Granulomatosis with Polyangiitis / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism / Q000503:physiopathology*; D053583:Interleukin-1beta / Q000032:analysis / Q000494:pharmacology; D016209:Interleukin-8 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology
chemical_list: D054365:Chemokine CXCL5; D053583:Interleukin-1beta; D016209:Interleukin-8; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor