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Understanding the mechanisms by which Reactive Oxygen Species (ROS) activate mononuclear phagocytes in inflammatory diseases of the lung.
Author(s) -
Wang Yijie,
Hunter Melissa G.,
Marsh Clay B.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1150
Subject(s) - phosphorylation , proto oncogene tyrosine protein kinase src , platelet derived growth factor receptor , kinase , protein kinase b , microbiology and biotechnology , mapk/erk pathway , tyrosine kinase , receptor tyrosine kinase , tyrosine phosphorylation , signal transduction , cancer research , biology , chemistry , receptor , growth factor , biochemistry
Previously, we found that ROS activated the Akt survival pathway and MAP kinases in monocytes. Thus, we hypothesized that ROS mediates signals through the activation of the macrophage colony‐stimulating factor receptor (M‐CSFR). In NIH 3T3 cells stably expressing the M‐CSFR, we found that H2O2 induced M‐CSFR phosphorylation and this phosphorylation event occurred in the absence of receptor dimerization suggesting that other kinases were involved. We examined the effect of either the general tyrosine kinase inhibitor genistein or the Src kinase inhibitor PP2. In the presence of the inhibitors, we found that H2O2‐induced phosphorylation of the M‐CSFR, Akt, and Erk was greatly reduced in NIH3T3/M‐CSFR cells and monocytes. Upon H2O2 stimulation of SYF fibroblast cell line that lacks Src kinases, phosphorylation of Akt and Erk was reduced compared to cells expressing c‐Src. A decrease in tyrosine phosphorylated proteins was observed in platelet derived growth factor (PDGF)‐treated SYF cells whereas expression of c‐Src restored activation. These observations suggest that ROS activate Src kinases to induce both PDGF and M‐CSF receptor activation and downstream signaling events. In monocytes, this occurs without receptor dimerization. We predict that these events result in prolonged activation of these cells and the development of inflammatory diseases within the lung.