Expression and function of receptors for the formylated peptides in granulocytes of the patients with rheumatoid arthritis

Formyl peptide receptors (FPRs) are an important part of innate immunity involved in antimicrobial phagocyte functions such as chemotaxis, secretory degranulation, and respiratory burst. These responses observed both acute systemic chronic inflammation. Abundant or constant release pro-inflammatory ligands leads to the pre-activation phagocytes when subsequent stimulation induces more intense cellular response. Binding formyl receptor with its agonist activates production reactive oxygen species, due triggering phosphorylation cytoplasmic subunits p47phox p67phox followed by their translocation plasma membrane assembly into NADPH oxidase complex. Rheumatoid arthritis is characterized imbalance immune processes autoimmune against own joint tissues. It known that, granulocytes produce increased amounts radicals various pathologies, including rheumatoid arthritis. We suggest that enhancement may be expression components FPR/PKC/NOX2 signaling pathway. Our aim was study mRNA fpr1/fpr2 genes FPR-dependent species isolated peripheral blood from patients Materials methods. The objects were granulocytes. analyzed, respectively, 166 85 samples healthy donors. assessed using luminol-dependent chemiluminescence. For FPR1 activation we used a distinct concentration fMLF: response it completely inhibited pretreatment cells antagonist N-t-boc-MLF. FPR2 performed synthetic WKYMVM, specific agonist. In arthritis, have revealed level spontaneous phorbol ester-induced granulocytes, thus reflecting pre-activated state found FPR1-mediated fpr1 gene patients. Furthermore, function associated constitutive FPR1/PKC/NOX2 pathway shown positive correlation between processes. induced also increased, but cannot directly attributed overexpression PKC/NOX2 activation, requires further study. Understanding mechanisms regulation cascades reveal new targets for anti-rheumatoid therapy.