BACKGROUND: Neutrophilic inflammation causes lung damage in cystic fibrosis (CF). Recent data from animal models suggest that the migration of blood monocytes into the airway supports neutrophil-mediated tissue injury. CF may therefore be associated with increased airway levels of chemoattractants for pro-inflammatory monocytes. In this study, we sought to assess the levels of monocyte chemoattractants CCL2 and CX3CL1 in the blood and airways of patients with CF, and expression of their respective receptors CCR2 and CX3CR1 on blood monocytes. METHODS: Blood was obtained from 32 CF patients and 25 healthy controls. Induced sputum was obtained from a further 24 CF patients and 17 healthy controls. Expression of CCR2 and CX3CR1 on CD14++CD16- and CD14+CD16+ blood monocytes was determined by flow cytometry. CCL2 and CX3CL1 levels in blood and induced sputum were determined by ELISA. RESULTS: Total blood monocyte concentration was not different between CF and controls. CCR2 was absent, and CX3CR1 higher on CD14+CD16+ monocytes from both CF and controls when compared with expression on CD14++CD16- cells. There was no difference in expression of chemokine receptors by either monocyte subpopulation between CF and controls. Blood CCL2, but not CX3CL1, was increased in CF patients (p = 0.006). Similarly, CF was associated with increased induced sputum CCL2, but not CX3CL1 (190.6 vs. 77.3pg/mL; p = 0.029). CONCLUSION: CCL2, but not CX3CL1 is increased in the airway and blood of CF patients. Blood monocytes from CF patients are phenotypically competent to respond to CCL2, since they express normal levels of CCR2.
BACKGROUND:Neutrophilic inflammation causes lung damage in cystic fibrosis (CF). Recent data from animal models suggest that the migration of blood monocytes into the airway supports neutrophil-mediated tissue injury. CF may therefore be associated with increased airway levels of chemoattractants for pro-inflammatory monocytes. In this study, we sought to assess the levels of monocyte chemoattractants CCL2 and CX3CL1 in the blood and airways of patients with CF, and expression of their respective receptors CCR2 and CX3CR1 on blood monocytes. METHODS: Blood was obtained from 32 CFpatients and 25 healthy controls. Induced sputum was obtained from a further 24 CFpatients and 17 healthy controls. Expression of CCR2 and CX3CR1 on CD14++CD16- and CD14+CD16+ blood monocytes was determined by flow cytometry. CCL2 and CX3CL1 levels in blood and induced sputum were determined by ELISA. RESULTS: Total blood monocyte concentration was not different between CF and controls. CCR2 was absent, and CX3CR1 higher on CD14+CD16+ monocytes from both CF and controls when compared with expression on CD14++CD16- cells. There was no difference in expression of chemokine receptors by either monocyte subpopulation between CF and controls. Blood CCL2, but not CX3CL1, was increased in CFpatients (p = 0.006). Similarly, CF was associated with increased induced sputum CCL2, but not CX3CL1 (190.6 vs. 77.3pg/mL; p = 0.029). CONCLUSION:CCL2, but not CX3CL1 is increased in the airway and blood of CFpatients. Blood monocytes from CFpatients are phenotypically competent to respond to CCL2, since they express normal levels of CCR2.
Authors: D W Russell; M Hardison; K R Genschmer; T Szul; P E Bratcher; M Abdul Roda; X Xu; L Viera; J E Blalock; A Gaggar; B D Noerager Journal: Biochem Biophys Res Commun Date: 2019-08-07 Impact factor: 3.575
Authors: Katherine B Hisert; Timothy P Birkland; Kelly Q Schoenfelt; Matthew E Long; Brenda Grogan; Suzanne Carter; W Conrad Liles; Edward F McKone; Lev Becker; Anne M Manicone; Sina A Gharib Journal: Front Pharmacol Date: 2020-08-13 Impact factor: 5.810