RATIONALE: There are increased neutrophils in the lungs of patients with chronic obstructive pulmonary disease (COPD), but it is unclear if this is due to increased inflammatory signal or related to the inherent behavior of the neutrophils. This is critical, because inaccurate or excessive neutrophil chemotaxis could drive pathological accumulation and tissue damage. OBJECTIVES: To assess migratory dynamics of neutrophils isolated from patients with COPD compared with healthy smoking and nonsmoking control subjects and patients with α(1)-antitryspin deficiency. METHODS: Migratory dynamics and structure were assessed in circulating neutrophils, using phase and differential interference contrast microscopy and time-lapse photography. The effect of COPD severity was studied. Surface expression of receptors was measured using flow cytometry. The in vitro effects of a phosphoinositide 3-kinase inhibitor (LY294002) were studied. MEASUREMENTS AND MAIN RESULTS: COPD neutrophils moved with greater speed than cells from either control group but with reduced migratory accuracy, in the presence of IL-8, growth-related oncogene α, formyl-methionyl-leucyl-phenylalanine, and sputum. This was present across all stages of COPD. Structurally, COPD neutrophils formed fewer pseudopods during migration. There were no differences in surface expression of the receptors CXCR1, CXCR2, or FPR1. LY294002 reduced COPD neutrophil migratory speed while increasing chemotactic accuracy, returning values to normal. The inhibitor did not have these effects in healthy control subjects or patients with a similar degree of lung disease. CONCLUSIONS: COPD neutrophils are intrinsically different than cells from other studied populations in their chemotactic behavior and migratory structure. Differences are not due to surface expression of chemoattractant receptors but instead appear to be due to differences in cell signaling.
RATIONALE: There are increased neutrophils in the lungs of patients with chronic obstructive pulmonary disease (COPD), but it is unclear if this is due to increased inflammatory signal or related to the inherent behavior of the neutrophils. This is critical, because inaccurate or excessive neutrophil chemotaxis could drive pathological accumulation and tissue damage. OBJECTIVES: To assess migratory dynamics of neutrophils isolated from patients with COPD compared with healthy smoking and nonsmoking control subjects and patients with α(1)-antitryspin deficiency. METHODS: Migratory dynamics and structure were assessed in circulating neutrophils, using phase and differential interference contrast microscopy and time-lapse photography. The effect of COPD severity was studied. Surface expression of receptors was measured using flow cytometry. The in vitro effects of a phosphoinositide 3-kinase inhibitor (LY294002) were studied. MEASUREMENTS AND MAIN RESULTS:COPD neutrophils moved with greater speed than cells from either control group but with reduced migratory accuracy, in the presence of IL-8, growth-related oncogene α, formyl-methionyl-leucyl-phenylalanine, and sputum. This was present across all stages of COPD. Structurally, COPD neutrophils formed fewer pseudopods during migration. There were no differences in surface expression of the receptors CXCR1, CXCR2, or FPR1. LY294002 reduced COPD neutrophil migratory speed while increasing chemotactic accuracy, returning values to normal. The inhibitor did not have these effects in healthy control subjects or patients with a similar degree of lung disease. CONCLUSIONS:COPD neutrophils are intrinsically different than cells from other studied populations in their chemotactic behavior and migratory structure. Differences are not due to surface expression of chemoattractant receptors but instead appear to be due to differences in cell signaling.
Authors: Eitan Halper-Stromberg; Jeong H Yun; Margaret M Parker; Ruth Tal Singer; Amit Gaggar; Edwin K Silverman; Sonia Leach; Russell P Bowler; Peter J Castaldi Journal: Am J Respir Cell Mol Biol Date: 2018-04 Impact factor: 6.914
Authors: Sebastián A Riquelme; Benjamin D Hopkins; Andrew L Wolfe; Emily DiMango; Kipyegon Kitur; Ramon Parsons; Alice Prince Journal: Immunity Date: 2017-12-12 Impact factor: 31.745
Authors: Aran Singanayagam; Nicholas Glanville; Leah Cuthbertson; Nathan W Bartlett; Lydia J Finney; Elena Turek; Eteri Bakhsoliani; Maria Adelaide Calderazzo; Maria-Belen Trujillo-Torralbo; Joseph Footitt; Phillip L James; Peter Fenwick; Samuel V Kemp; Thomas B Clarke; Jadwiga A Wedzicha; Michael R Edwards; Miriam Moffatt; William O Cookson; Patrick Mallia; Sebastian L Johnston Journal: Sci Transl Med Date: 2019-08-28 Impact factor: 17.956