Functional KCa 3.1 K+ channels are required for human fibrocyte migration

• Published in: Journal of allergy and clinical immunology 2011, Vol.128 (6), p.1303-1309.e2
• Main Authors: Cruse, Glenn, PhD, Singh, Shailendra R., PhD, Duffy, S. Mark, PhD, Doe, Camille, BSc, Saunders, Ruth, PhD, Brightling, Chris E., PhD, Bradding, Peter, DM
• Format: Article
• Language: English
• Subjects: Allergy and Immunology
• ISSN: 0091-6749
• DOI: 10.1016/j.jaci.2011.07.047

Background Fibrocytes are bone marrow–derived CD34+ collagen I–positive cells present in peripheral blood that develop α-smooth muscle actin expression and contractile activity in tissue culture. They are implicated in the pathogenesis of tissue remodeling and fibrosis in both patients with asthma and those with idiopathic pulmonary fibrosis. Targeting fibrocyte migration might therefore offer a new approach for the treatment of these diseases. Ion channels play key roles in cell function, but the ion-channel repertoire of human fibrocytes is unknown. Objective We sought to examine whether human fibrocytes express the KCa 3.1 K+ channel and to determine its role in cell differentiation, survival, and migration. Methods Fibrocytes were cultured from the peripheral blood of healthy subjects and patients with asthma. Whole-cell patch-clamp electrophysiology was used for the measurement of ion currents, whereas mRNA and protein were examined to confirm channel expression. Fibrocyte migration and proliferation assays were performed in the presence of KCa 3.1 ion-channel blockers. Results Human fibrocytes cultured from the peripheral blood of both healthy control subjects and asthmatic patients expressed robust KCa 3.1 ion currents together with KCa 3.1 mRNA and protein. Two specific and distinct KCa 3.1 blockers (TRAM-34 and ICA-17043) markedly inhibited fibrocyte migration in transwell migration assays. Channel blockers had no effect on fibrocyte growth, apoptosis, or differentiation in cell culture. Conclusions The K+ channel KCa 3.1 plays a key role in human fibrocyte migration. Currently available KCa 3.1-channel blockers might therefore attenuate tissue fibrosis and remodeling in patients with diseases such as idiopathic pulmonary fibrosis and asthma through the inhibition of fibrocyte recruitment.