Chemokine clinical relevance

Locati, M., and Murphy, P. M. (1999). Chemokines and chemokine receptors Biology and clinical relevance in inflammation and AIDS. Annu. Rev. Med. 50, 425-440. 

Part II of the book explores the role of chemokines in a variety of chronic and acute inflammatory diseases, including acute respiratory distress syndrome (ARDS), asthma, interstitial lung disease, rheumatoid arthritis, and organ transplant rejection. These topics are discussed through a presentation of the pathogenesis of the disease, using a wide range of clinically relevant animal models of the disease, as well as the examination of chemokine expression in clinical samples. 

The gold-standard assay used for all chemokine receptor inhibitors that reach clinical-phase trials is the chemotaxis functional assay. This assay relies on the ability of chemokines to recruit cells expressing their respective receptor to areas of inflammation. In vitro, this assay was first described in detail by Taub et al. (16) for 24/48-well plates currently, this can be achieved by using 96-well plates. Cells are incubated in the upper chamber with an antagonist for a particular receptor (at different concentrations or with buffer) and challenged to migrate to the lower chamber, which has the relevant chemokine. After 2 to 4 hours of incubation at 37°C, the upper chamber inlet is removed and the cells in the lower chamber quantified by fluorescence with, for example, Calcein AM (Invitrogen, Carlsbad, CA). 

---