The effects of c-reactive protein (CRP) isoforms on inflammation and wound healing processes

C-reactive protein (CRP) is a homopentameric acute-phase inflammatory protein that exhibits elevated expression during inflammation. CRP can be found in its pentameric form (nCRP) or monomeric form (mCRP). To date there has been little research investigating the effects of these CRP isoforms in wound healing processes and age-related impaired healing, which is known to have an altered inflammatory response. The study investigated CRP isoform localisation in murine wounds (detected by immunohistochemistry) and circulating blood (measured by immunoblotting) using models of acute healing in young adults and age-related impaired healing (n=3). Using in vitro inflammatory cell assays developed with the monocytic U937 cell line this study investigated the effects of CRP isoforms in nitric oxide release (detected by an immunoassay), phagocytosis (measured by a bacterial recovery assay), apoptosis (detected via DNA fragmentation) and cytokine secretion (measured by a multiplex immunoassay) in both monocyte and macrophage-like cells (n=6). Pharmacological inhibitors were used to determine the potential CRP-induced pathways or mechanisms. Both isoforms were localised to sites of inflammation, implying that they may play an active inflammatory role during wound repair. Moreover, the ratio of CRP isoforms (mCRP:nCRP) reflected the degree of inflammation, with higher values indicating elevated mCRP localisation and pronounced inflammation in the model of age-related impaired healing. In in vitro inflammatory cell assays, nCRP exhibited a more anti-inflammatory effect leading to significantly (P=0.01) increased phagocytosis, increased apoptosis, decreased nitric oxide (NO) production, and reduced overall pro-inflammatory cytokine production in monocytes and macrophages. The mCRP isoform significantly (P