Abstract
IntroductionGelsolin is an intracellular actin-binding protein involved in cell shape changes, cell motility, and apoptosis. An extracellular gelsolin isoform, plasma gelsolin circulates in the blood of healthy individuals at a concentration of 200 ± 50 mg/L and has been suggested to be a key component of an extracellular actin-scavenging system during tissue damage. Levels of plasma gelsolin decrease during acute injury and inflammation, and administration of recombinant plasma gelsolin to animals improves outcomes following sepsis or burn injuries. In the present study, we investigated plasma gelsolin in patients with rheumatoid arthritis.MethodsCirculating and intra-articular levels of plasma gelsolin were measured in 78 patients with rheumatoid arthritis using a functional (pyrene-actin nucleation) assay and compared with 62 age- and gender-matched healthy controls.ResultsCirculating plasma gelsolin levels were significantly lower in patients with rheumatoid arthritis compared with healthy controls (141 ± 32 versus 196 ± 40 mg/L, P = 0.0002). The patients' intra-articular plasma gelsolin levels were significantly lower than in the paired plasma samples (94 ± 24 versus 141 ± 32 mg/L, P = 0.0001). Actin was detected in the synovial fluids of all but four of the patients, and immunoprecipitation experiments identified gelsolin-actin complexes.ConclusionsThe plasma isoform of gelsolin is decreased in the plasma of patients with rheumatoid arthritis compared with healthy controls. The reduced plasma concentrations in combination with the presence of actin and gelsolin-actin complexes in synovial fluids suggest a local consumption of this potentially anti-inflammatory protein in the inflamed joint.
Highlights
Gelsolin is an intracellular actin-binding protein involved in cell shape changes, cell motility, and apoptosis
Circulating plasma gelsolin levels were significantly lower in patients with rheumatoid arthritis compared with healthy controls (141 ± 32 versus 196 ± 40 mg/L, P = 0.0002)
The plasma isoform of gelsolin is decreased in the plasma of patients with rheumatoid arthritis compared with healthy controls
Summary
Gelsolin is an intracellular actin-binding protein involved in cell shape changes, cell motility, and apoptosis. Plasma gelsolin (pGSN) is the extracellular isoform of a ubiquitous cytoplasmic actin-binding protein, gelsolin (GSN), that mediates cell shape changes and motility [1]. The unifying explanation for low pGSN concentrations in acute inflammatory conditions is the exposure by injury to plasma of the GSN-binding ligand, actin, a major cellular constituent ordinarily separated from the extracellular environment by intact plasma membranes. In some but not all such cases of cGSN: cytoplasmic gelsolin; cMMP-3: catalytic domain of matrix metalloproteinase-3; CRP: C-reactive protein; DMARD: disease-modifying anti-rheumatic drug; F-actin: filamentous actin; GSN: gelsolin; HRP: horseradish peroxidase; IL-6: interleukin-6; MMP: matrix metalloproteinase; MTX: methotrexate; pGSN: plasma gelsolin; PVDF: polyvinylidene difluoride; RA: rheumatoid arthritis; rhpGSN: recombinant human plasma gelsolin; SB: sample buffer; SF: synovial fluid
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