Related Experiment Videos
Cell-derived microparticles in synovial fluid from inflamed arthritic joints support coagulation exclusively via a
René J Berckmans1, Rienk Nieuwland, Paul Peter Tak
1Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. r.j.berckmans@amc.uva.nl
Objective:
To determine the cellular origin of synovial microparticles, their procoagulant properties, and their relationship to local hypercoagulation.
Methods:
Microparticles in synovial fluid and plasma from patients with rheumatoid arthritis (RA; n = 10) and patients with other forms of arthritis (non-RA; n = 10) and in plasma from healthy subjects (n = 20) were isolated by centrifugation. Microparticles were identified by flow cytometry. The ability of microparticles to support coagulation was determined in normal plasma. Concentrations of prothrombin fragment F(1+2) (by enzyme-linked immunosorbent assay [ELISA]) and thrombin-antithrombin (TAT) complexes (by ELISA) were determined as estimates of the coagulation activation status in vivo.
Results:
Plasma from patients and healthy controls contained comparable numbers of microparticles, which originated from platelets and erythrocytes. Synovial microparticles from RA patients and non-RA patients originated mainly from monocytes and granulocytes; few originated from platelets and erythrocytes. Synovial microparticles bound less annexin V (which binds to negatively charged phospholipids) than did plasma microparticles, exposed tissue factor, and supported thrombin generation via factor VII. F(1+2) (median 66 nM) and TAT complex (median 710 microg/liter) concentrations were elevated in synovial fluid compared with plasma from the patients (1.6 nM and 7.0 microg/liter, respectively) as well as the controls (1.0 nM and 2.9 microg/liter, respectively).
Conclusion:
Synovial fluid contains high numbers of microparticles derived from leukocytes that are strongly coagulant via the factor VII-dependent pathway. We propose that these microparticles contribute to the local hypercoagulation and fibrin deposition in inflamed joints of patients with RA and other arthritic disorders.
Insights
Synovial microparticles in arthritis originate from leukocytes and promote blood clotting. These leukocyte-derived microparticles contribute to local hypercoagulation in inflamed joints.
Area of Science:
- Rheumatology
- Hematology
- Cell Biology
Background:
- Synovial microparticles are implicated in joint inflammation.
- Their cellular origin and procoagulant activity in arthritis are not fully understood.
Purpose of the Study:
- To identify the cellular origin of synovial microparticles.
- To assess their procoagulant properties.
- To investigate their role in local hypercoagulation in arthritis.
Main Methods:
- Microparticles isolated from synovial fluid and plasma of rheumatoid arthritis (RA) and non-RA patients, and healthy controls.
- Flow cytometry used for microparticle identification.
- Coagulation support, tissue factor exposure, and coagulation activation markers (F(1+2), TAT complexes) measured.
Main Results:
- Synovial microparticles primarily derived from monocytes and granulocytes, unlike plasma microparticles (platelets, erythrocytes).
- Synovial microparticles exposed tissue factor and supported thrombin generation.
- Elevated prothrombin fragment F(1+2) and thrombin-antithrombin complexes found in synovial fluid, indicating local hypercoagulation.
Conclusions:
- Synovial fluid contains abundant, procoagulant leukocyte-derived microparticles.
- These microparticles activate coagulation via the factor VII-dependent pathway.
- They likely contribute to hypercoagulation and fibrin deposition in inflamed arthritic joints.