PT  - JOURNAL ARTICLE
AU  - A.G. Richter
AU  - G.D. Perkins
AU  - A. Chavda
AU  - E. Sapey
AU  - L. Harper
AU  - D.R. Thickett
TI  - Neutrophil chemotaxis in Wegener's granulomatosis and idiopathic pulmonary fibrosis
AID  - 10.1183/09031936.00161910
DP  - 2011 Sep 01
TA  - European Respiratory Journal
PG  - erj01619-2010
4099  - http://erj.ersjournals.com/content/early/2011/09/01/09031936.00161910.short
4100  - http://erj.ersjournals.com/content/early/2011/09/01/09031936.00161910.full
AB  - The presence of anti-neutrophil cytoplasmic antibodies (ANCA) in Wegener's granulomatosis (WG), implicate 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 WG lung are unknown.BALF cell counts, myeloperoxidase (MPO) and chemokines were measured in 27 patients with WG, 20 disease controls with idiopathic pulmonary fibrosis (IPF) and 6 healthy controls. CXCL-8, IL-1β, ENA-78, G-CSF and GM-CSF were measured by ELISA. The neutrophil chemotactic potential of BALF was investigated using the under agarose method and specific antibodies examined the role of CXCL-8 and IL-1β.WG BALF had an increased neutrophil percentage and elevated MPO, CXCL-8 and G-CSF concentrations compared with healthy controls. Chemotaxis of control neutrophils towards BALF from patients with active (p=0.006) and remission WG (p=0.077) and IPF patients (p=0.001) was increased compared with normal controls. BALF induced chemotaxis correlated with BALF IL-1β (r=0.761,p=0.001) and CXCL-8 (r=0.640,p=0.012) in WG and was inhibited by anti-CXCL-8 (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. CXCL-8 and IL-1β appear to play important roles in the neutrophil chemotactic response to BALF.