IL-5 induces leukotriene receptor expression
- Andrea Heinzmann1
© Biomed Central Ltd 2001
Received: 13 November 2000
Accepted: 19 September 2001
Published: 19 September 2001
Leukotrienes are important mediators in the pathogenesis of acute bronchoconstriction, chronic airway inflammation and persistent eosinophilia in the airways and blood of asthmatics. The main source of leukotrienes in the asthmatic lung is the eosinophil. Recently the receptor for leukotriene (LT) D4 (CysLT1R) was characterized and its expression on HL-60/eos cells was shown. Interleukin (IL)-5 is an important regulator of many eosinophil functions including chemotaxis, degranulation, and adhesion. This study used the model of HL-60/eos cells to determine the influence of IL-5 on the expression and function of CysLT1R in eosinophils.
IL-5 induced a concentration- and time-dependent augmentation of CysLT1R mRNA expression in HL-60/eos cells. The accumulation of CysLT1R mRNA was abrogated by pretreatment of the cells with actinomycin D (an inhibitor of RNA synthesis), suggesting an enhancement of transcription as the underlying mechanism. Furthermore, IL-5-induced transcription of CysLT1R mRNA was associated with an increased expression of CysLT1R protein on the cell surface of HL-60/eos cells. The up-regulation of CysLT1R expression led to an elevated calcium flux in response to LT D4 and an enhanced chemotactic response of HL-60/eos to LT D4 - thus demonstrating the functional importance of the IL-5 induced CysLT1R expression.
This paper presents a new pathophysiologic mechanism by which IL-5 exerts its role on eosinophils and provides further insight into the involvement of IL-5 in the pathogenesis of asthma and allergic diseases. IL-5 modulates the expression of CysLT1R and thus determines the response of eosinophils to LT D4, a potent stimulator of the inflammatory response. As shown in previous studies, IL-5 activates several other proteins involved in eosinophil growth and differentiation. The possible complex interaction of these proteins with the observed upregulation of CysLT1R by IL-5 requires further investigation. The knowledge of the exact pathway by which leukotrienes and their receptors are involved in the regulation of the immune response is especially important to enable the responsible use of leukotriene receptor antagonists in the treatment of asthma.
HL-60 cells, RT-PCR, northern blot, flow cytometry, Ca2+ mobilization assay, chemotaxis assay