Kallikreins, kininogens and kinin receptors on circulating and synovial fluid neutrophils: role in kinin generation in rheumatoid arthritis

B. Cassim, O.M. Shaw, M. Mazur, Neil Misso, A. Naran, D.R. Langlands, Philip Thompson, Kanti Bhoola

    Research output: Contribution to journalArticlepeer-review

    37 Citations (Scopus)

    Abstract

    Objectives. Neutrophils traffic into and have the capacity to generate kinins in SF of RA patients. The aim of this study was to assess the expression of kallikreins, kininogens and kinin receptors in circulating and SF neutrophils, as well as synovial tissue of RA patients, and to assess kinin generation in SF.Methods. Neutrophils were isolated from blood and SF of RA patients and blood of healthy volunteers. Expression of kallikreins, kininogens and kinin receptors in neutrophils and synovial tissue was assessed by immunocytochemistry using specific antibodies, with visualization by brightfield and confocal microscopy. Levels of basal and generated kinins in SF of RA patients were measured by ELISA.Results. Kinin labelling was significantly reduced, indicating the loss of the kinin moiety from kininogen on circulating (P <0.001) and SF neutrophils (P <0.05) of RA patients. Immunolabelling of tissue kallikrein was also decreased, whereas kinin B1 and B2 receptor expression was increased in circulating and SF neutrophils of RA patients. Immunolabelling of kallikreins and kinin receptor proteins was similar in RA and normal synovial tissues. The basal kinin level in SF of RA patients was 5.7 ± 6.1 ng/ml and the mean concentration of kinins generated in vitro was 80.6 ± 56.3 ng/ml. The capacity for kinin generation was positively correlated with measures of disease activity.Conclusions. Kallikrein–kinin proteins on neutrophils play an important role in kinin generation and the pathophysiology of RA. Specific kallikrein and kinin receptor antagonists may be useful as IA therapies for inflamed joints.
    Original languageEnglish
    Pages (from-to)490-496
    JournalRheumatology
    Volume48
    Issue number5
    DOIs
    Publication statusPublished - 2009

    Fingerprint

    Dive into the research topics of 'Kallikreins, kininogens and kinin receptors on circulating and synovial fluid neutrophils: role in kinin generation in rheumatoid arthritis'. Together they form a unique fingerprint.

    Cite this