The neutrophilia

in BALF, which is often found in IPF and pulmonary stage IV in sarcoidosis, could be responsible for the elevated MRP14 levels seen in patients. However, BALF MRP14 levels were associated much more strongly with pulmonary stage in sarcoidosis than the neutrophil percentage. This suggests that MRP14 is a more specific biomarker for pulmonary disease severity in sarcoidosis than the amount of neutrophils in BALF. In addition, we observed a correlation between MRP14 and BALF neutrophils in IPF patients, but it was small, and no such correlation was found in sarcoidosis patients. The lack of correlation with neutrophils in sarcoidosis indicates that high BALF MRP14 levels Idasanutlin price do not simply reflect the presence of neutrophils in the lung, although all the MRP proteins together make up approximately 50% of the neutrophils cytosolic protein content [22]. Previous reports on a possible chemoattractant role for MRP14 are ambiguous. A study by Ryckman et al. [10] LY2109761 reported that MRP8, MRP14 and the heterocomplex MRP8/14 caused neutrophil chemotaxis in vitro and in vivo, and the same group also reported that antibodies against MRP14 blocked neutrophil recruitment [23]. However, other studies reported that MRP14 was not a chemoattractant for neutrophils and even repelled neutrophils [24,25]. Our data do not support a possible chemoattractant role for MRP14, but do not rule out the possibility

that MRP14 is a chemoattractant for neutrophils under specific conditions; for instance, in some IPF patients. An mRNA expression study in rabbits showed that after neutrophils migrate from the blood to inflammatory Branched chain aminotransferase sites the mRNA expression of MRP14 increases rapidly [26]. In addition, neutrophilic MRP14 is phosphorylated and translocated to the membrane during human neutrophil activation [27]. This suggests that MRP14 levels during inflammatory reactions are not dependent on the number of neutrophils present, but rather on their activity. Activated neutrophils can cause lung injury, epithelial cell apoptosis and basement membrane loss [28,29]. Neutrophils are also thought to mediate the transition from acute to chronic inflammation that may precede fibrosis [30]. Both neutrophils and macrophages have been reported to have an altered phenotype in the lungs of sarcoidosis patients [31,32]. It is possible that MRP14 is a marker for an activated subset of leucocytes. Further research is needed to reveal whether MRP14 expression is upregulated in neutrophils and alveolar macrophages in interstitial lung diseases. It is intriguing to speculate about the exact role of MRP14. It may influence the functioning of leucocytes in several ways. For instance, a study by Newton and Hogg showed that MRP14 could be involved in the attachment of neutrophils to the endothelium, and could thus facilitate their migration [24].