Although several clinical studies have observed elevated extracellular GrK in disease, this is the first study to demonstrate a physiological role for extracellular GrK in cytokine production. The observation that GrK can initiate cytokine release and induce cell proliferation in lung fibroblasts is significant given recent observations that extracellular GrK is detected in the BAL of patients with viral pneumonia and allergic asthma [10,11]. IL-6, IL-8 and MCP-1 are important mediators in the regulation of the acute-phase response to injury and infection by influencing immune cell recruitment, as well as the differentiation and activation of T cells and macrophages [43,44,45]. In the current study, elevated levels of MCP-1 were detected in supernatants following treatment with low concentrations of GrK. MCP-1 is expressed by numerous cell types, including monocytes/macro- phages, fibroblasts, and epithelial cells, and is a potent chemoat- tractant for mononuclear cells. 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Borensztajn K, Stiekema J, Nijmeijer S, Reitsma PH, Peppelenbosch MP, et al. (2008) Factor Xa stimulates proinflammatory and profibrotic responses in fibroblasts via protease-activated receptor-2 activation. Am J Pathol 172: 309–320. PLoS ONE | www.plosone.org 8 June 2011 | Volume 6 | Issue 6 | e21484