Epithelial Anion Transport as Modulator of Chemokine Signaling

Figure 2

Putative mechanisms linking impaired anion transport to augmented epithelial chemokine signaling in secretory epithelia. (a) Low ASL in CF results in elevated concentrations of CXCL chemokines due to the reduced liquid volume in the luminal compartment. The increased concentration gradient enhances the neutrophil chemotaxis [250]. (b) Low ASL pH may directly activate chemokine expression by activating acid-sensing signaling pathways via proton-sensing GPCRs, ErbB1, and ErbB2 or the soluble protein SPLUNC1. (c) The decreased ROS buffering capacity of the ASL due to the reduced GSH concentration may promote hydrogen peroxide (H₂O₂) mediated metalloproteinase (MMP) activation. These in turn cleave pro-erbB1 ligands resulting in erbB1 activation, thus initiating signaling pathways that lead to the upregulation of chemokine expression [285].

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