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Chemokine Concentrations and Mast Cell Chemotactic Activity in BAL Fluid in Patients With Eosinophilic Bronchitis and Asthma, and in Normal Control Subjects^*

^* From the Institute for Lung Health (Ms. Woodman, Ms. Sutcliffe, Drs. Kaur, Bradding, Brightling, and Berry), University of Leicester, Leicester, UK; and Department of Respiratory Medicine (Dr. Pavord), University Hospitals of Leicester, Leicester, UK.

Correspondence to: Christopher E. Brightling, PhD, Insitute for Lung Health, University of Leicester, Glenfield Hospital, Groby Rd, Leicester LE3 9QP, UK; e-mail: ceb17{at}le.ac.uk

Abstract

Background: Asthma and eosinophilic bronchitis share many immunopathologic features including increased numbers of eosinophils and mast cells in the superficial airway. The mast cell chemotactic activity of airway secretions has not been assessed in patients with eosinophilic bronchitis.

Objectives: To investigate the concentration of chemokines in bronchial wash samples and BAL fluid, and the mast cell chemotactic activity in BAL fluid from subjects with asthma and eosinophilic bronchitis, and from healthy control subjects.

Methods: We measured the concentrations of CCL11, CXCL8, and CXCL10 in bronchial wash samples and BAL fluid from 14 subjects with eosinophilic bronchitis, 14 subjects with asthma, and 15 healthy control subjects. Mast cell chemotaxis to BAL fluid from these subjects was examined using the human mast cell line HMC-1.

Results: The bronchial wash sample and BAL fluid concentrations of CXCL10 and CXCL8 was increased in subjects with eosinophilic bronchitis compared to those in subjects with asthma and healthy control subjects (p < 0.05). The CCL11 concentration was below the limit of detection in most subjects. BAL fluid from subjects with eosinophilic bronchitis was chemotactic for mast cells (1.4-fold migration compared to a control, 95% confidence interval, 1.1 to 1.9; p = 0.04) and was inhibited by blocking CXCR1 (45% inhibition; p = 0.002), CXCR3 (38% inhibition; p = 0.034), or both (65% inhibition; p = 0.01). BAL fluid from the subjects with asthma and healthy control subjects was not chemotactic for mast cells. Mast cell migration to BAL fluid was correlated with the concentration of CXCL8 (r = 0.42; p = 0.031) and CXCL10 (r = 0.52; p = 0.007).

Conclusion: In subjects with eosinophilic bronchitis, CXCL8 and CXCL10 concentrations were elevated in airway secretions. These chemokines may play a key role in mast cell recruitment to the superficial airway in this condition.

Key Words: CCL11 • CCR3 • chemokine receptor • CXCL8 • CXCL10 • CXCR1 • CXCR3