ABSTRACT
This review aims to cast a look at endometriosis as a chronic and progressive gynecological disease.Endometriosis-affected tissues show a variety of pathologic features: alterations in cell growth, apoptosis, activation, angiogenesis, cell adhesion, and cytokine production. Fresh endometriotic lesions are associated with induction of an inflammatory reaction represented by overproduction of prostaglandins (PGE2), metalloproteinases (MMP-2, -3, -9), cytokines (IL-1ß, IL-8, IFN-γ, TNF-α, MCP-1 and MIF) and adhesive molecules (ICAM-1, VCAM-1) and activation of synthesis of reactive oxygen and nitrogen species. The inflammatory process may lead to defective folliculogenesis by an altered follicular milieu. An increase in the number and change in function of macrophages, T- and B-lymphocytes and reduction of NK cells have been reported. Treg lymphocytes are known to play an extremely important role in controlling and modulating changes in the aberrant immune response in endometriosis. Dysregulation of the immune system results in both increased progression of endometriosis and its severity. In inflammatory conditions the immune cells provide immune defense at the local level - in peritoneal fluid - and could further cause: 1) a decrease of the number of NK CD16+ cells with expression of KIRs and an increase of NK CD57+; 2) increased numbers of CD8+ cells and CD11b- immature dendritic cells; 3) an increase of FoxP3 expression in the regulatory T cell (Treg) population; 4) an increase of macrophages activating T- and B-lymphocytes leading to elevated synthesis of cytokines and/or autoantibodies. We may conclude that endometriosis resembles an immunodependent disease with the autoimmune background and breakdown of immunosuppressive mechanisms. Further immunological investigations may open a new avenue to discover innovative immunomodulatory treatments of endometriosis.
ABSTRACT
Rheumatoid arthritis (RA) is a progressive chronic inflammatory and autoimmune joint disease. Neutrophils and monocytes are the main target cells of innate immune defense that modulate the course of inflammatory rheumatic diseases. Dysfunctional phagocytosis is a common feature in RA. The aim of this study was to evaluate the diagnostic value of apoptotic changes in neutrophils and monocytes and their relationship with rheumatoid activity measured by the DAS28 score. We used the APOLECT flow cytometric assay for evaluating primary necrotic, apoptotic, and secondary necrotic neutrophils and monocytes determination in RA patients compared with healthy controls. The apoptotic granulocytes were greater in RA patients compared to healthy controls (0.76 ± 0.15% vs. 0.58 ± 0.17%, P < 0.05). The percentage of primary necrotic granulocytes was significantly elevated in RA patients compared to healthy controls (3.84 ± 0.5% vs. 1.96 ± 0.33%). No significant difference was noted for primary necrotic monocytes. The number of secondary necrotic granulocytes and monocytes was high in RA patients (0.94 ± 0.15% vs. 0.4 ± 0.06% and 4.83 ± 1.06% vs. 1.8 ± 0.33%, respectively). The obtained results suggest that neutrophils and monocytes undergo apoptotic modifications which are accompanied by secondary necrotic cells formation in RA. These shifts may lead to autoantigen accumulation that results in the progressive course RA.