C-reactive protein mediates CD11b expression in monocytes through the non-receptor tyrosine kinase, Syk, and calcium mobilization but not through cytosolic peroxides

C-Reactive protein (CRP) can modulate integrin surface expression on monocytes following Fcgamma receptor engagement. We have investigated the signal transduction events causing this phenotypic alteration. CRP-induced signalling events were examined in THP-1 and primary monocytes, measuring Syk phosphorylation by Western blotting, intracellular Ca(2+) ([Ca(2+)](i)) by Indo-1 fluorescence and surface expression of CD11b by flow cytometry. Cytosolic peroxides were determined by DCF fluorescence. CRP induced phosphorylation of Syk and an increase in [Ca(2+)](i) both of which were inhibitable by the Syk specific antagonist, piceatannol. Piceatannol also inhibited the CRP-induced increase in surface CD11b. In addition, pre-treatment of primary monoytes with the Ca(2+) mobiliser, thapsigargin, increased CD11b expression; this effect was accentuated in the presence of CRP but was abolished in the presence of the [Ca(2+)](i) chelator, BAPTA. CRP also increased cytosolic peroxide levels; this effect was attenuated by antioxidants (ascorbate, alpha-tocopherol), expression of surface CD11b not being inhibited by antioxidants alone. CRP induces CD11b expression in monocytes through a peroxide independent pathway involving both Syk phosphorylation and [Ca(2+)](i) release.