Biomedical subjects

Maria I Bokarewa

Publications and source records attributed to Maria I Bokarewa.

3 recordsLinked to original sources

PubMed2003

Intraarticular release and accumulation of defensins and bactericidal/permeability-increasing protein in patients with rheumatoid arthritis.

OBJECTIVE: Defensins and bactericidal/permeability-increasing protein (BPI) are the components of the azurophilic granules of polymorphonuclear cells (PMNC) maintaining antimicrobial protection. Both these substances have been suggested to interact with the host immune system rather than merely kill invading pathogens. We assessed concentrations of BPI and a-defensins in synovial fluid (SF) and matching blood samples of patients with rheumatoid arthritis (RA). METHODS: Matching samples of SF and blood were collected from 67 patients with RA (aged 21-73 yrs) with acute joint effusion. Blood samples from 22 healthy individuals made up a control group. Concentrations of BPI and human neutrophil peptides (HNP 1-3) were measured by ELISA. The results were related to radiological signs of destructive arthritis, duration of the disease, and laboratory markers of inflammation. RESULTS: BPI and HNP concentrations in SF were 10-60 times higher than in matching blood samples (p < 0.0001). Strong correlations between BPI and HNP concentrations were found in both blood and SF. In SF, BPI and HNP concentrations correlated to white blood cell (WBC) count (p < 0.001), and were associated with erosive joint disease (p < 0.05). In contrast, WBC count, serum C-reactive protein, or rheumatoid factor were not significantly correlated to the BPI or HNP concentrations. Serum BPI concentrations were moderately but significantly increased in RA patients compared in blood to controls (p < 0.05). CONCLUSION: BPI and HNP are accumulated in the synovial cavity of patients with RA. Significant correlation between joint erosion and local occurrence of BPI and HNP suggests participation of these molecules in regulation of the destructive course of RA.

Adult↗

PubMed2002

Tissue factor as a proinflammatory agent.

Tissue factor (TF) is a transmembrane glycoprotein and the main triggering element of blood coagulation. TF expression on monocytes and endothelial cells is induced by exposure to endotoxin, tumor necrosis factor, and IL-1 and is considered to appear in consequence of inflammation. In order to assess the proinflammatory capacity of TF itself, the recombinant extracellular domain of TF was injected intra-articularly into healthy mice. To characterize the role of immune cells in the TF-induced arthritis, mice deprived of lymphocytes, neutrophils and monocytes were used. Histomorphological analysis of the joints with respect to inflammatory cell infiltration, pannus formation and erosion formation revealed development of arthritis in 80% of animals injected with TF. In most of the cases synovial proliferation was accompanied by pannus formation and cartilage destruction. Inflammatory cell infiltrate consisted of CD4-Mac1+ macrophages. Depletion of monocytes was, however, not enough to abolish inflammation. Indeed, combined deficiency of monocytes and lymphocytes was required to prevent inflammation following the injection of TF. We observed that TF induced chemokine production (MIP-1alpha and RANTES), but did not induce a proliferative response nor cytokine release by mouse spleen cells. TF has strong inflammatogenic properties mediated predominantly by monocytes and their release of chemokines. Our study shows that TF can simultaneously trigger the immune and coagulation systems.

Animals↗

PubMed2002

Phosphorotioated oligonucleotides trigger synthesis of human coagulation serine proteases.

RATIONALE: CpG containing phosphorotioated oligonucleotides (ODN) are efficient adjuvants able to enhance macrophage and B cell activities. Their impact in the generation of coagulation and fibrinolytic factors has not been analysed. OBJECTIVES: Production of coagulation and fibrinolytic proteins by human peripheral blood mononuclear cells (PBMC) treated with ODN was assessed. FINDINGS: ODN induced in vitro generation of tissue factor (TF), thrombin and plasminogen, by PBMC. Synthesis of TF and thrombin occurred mostly in monocytes, while plasminogen was produced by both monocytic and lymphocytic cell populations. Generation of these proteins stimulated by CpG was totally blocked by cycloheximide, indicating the requirement of ongoing protein synthesis. Protein synthesis was equally pronounced at stimulation with cytosine-phosphate-guanosine (CpG)- and GpC-containing ODN, and depended on the presence of the phosphorotioate moiety backbone in the ODN. Plasminogen, synthesized by monocytes and lymphocytes, was shown to be the primary product of ODN activation, leading subsequently to the expression of TF and thrombin generation. CONCLUSIONS: Our findings should be taken into consideration when assessing advantages and drawbacks of immunotherapy and gene therapy.

Adult↗