Functional K_Ca3.1 K⁺ channels are required for human fibrocyte migration

详细信息    查看全文

• 作者：Glenn Cruse PhD^&lowast ; ; Shailendra R. Singh PhD^&lowast ; ; S. Mark Duffy PhD^&lowast ; ; Camille Doe BSc ; Ruth Saunders PhD ; Chris E. Brightling PhD ; Peter Bradding DM  ; ;   ; ^{pbradding@hotmail.com}
• 关键词：Pulmonary fibrosis ; asthma ; fibrocyte ; cell migration ; ion channel ; K_Ca3.1 ; patch clamp electrophysiology
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2011
• 出版时间：December 2011
• 年：2011
• 卷：128
• 期：6
• 页码：1303-1309.e2
• 全文大小：730 K

文摘

Background

Fibrocytes are bone marrow¨Cderived CD34⁺ collagen I¨Cpositive cells present in peripheral blood that develop ¦Á-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 K_Ca3.1 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 K_Ca3.1 ion-channel blockers.

Results

Human fibrocytes cultured from the peripheral blood of both healthy control subjects and asthmatic patients expressed robust K_Ca3.1 ion currents together with K_Ca3.1 mRNA and protein. Two specific and distinct K_Ca3.1 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 K_Ca3.1 plays a key role in human fibrocyte migration. Currently available K_Ca3.1-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.