engleski

4-HYDROXY 2-NONENAL IN PATHOGENESIS OF OSTEOARTHRYTIS

Stress on joint tissues and metabolic processes leads to low grade inflammation in joint with osteoarthritis (OA). Inflammation generates free radicals, which damage polyunsaturated fatty acids. The most abundant product of free radical reactions is tremendously reactive 4-hydroxy 2-nonenal (HNE), which exerts cyotoxic effects at the site of generation on a dose dependent manner. HNE promotes survival and proliferation by induction of NFB signalling pathway and downstream pro-inflammatory mediator-expressions, supporting cell activation. At higher concentrations, HNE activates caspases and DNA fragmentation. The aim of our study was to investigate the presence of HNE in synovial tissue of OA patients in respect to M1/M2 polarisation of macrophages. We used immunohistology and/or double immunofluorescence techniques for antigens detection in paraffin embedded mature synovial tissue, obtained during the knee alloarthroplasty. HNE was homogenously expressed in cytoplasm of accumulated CD68+ macrophages and lymphocytes, mostly of CD56+ phenotype, together with the expression of pro-survival NFB. Apoptotic protease activating factor 1, which initiates an apoptotic protease cascade, appeared less often as nuclear granular pattern of labelling. In leukocyte infiltrations, we proved more iNOS+IL-15+CCL2+TNF-+ CD68 expressing M1 macrophages, while M2 polarisation markers arginase-1 and CCL22 were absent. In contrast, CD68+ macrophages scattered in sublining synovial tissue were strongly arginase-1 positive, indicating their M2 polarisation. In conclusion, HNE might be involved in supporting pro-inflammatory reactions within synovial tissue leukocyte infiltration governing domination of M1 over M2 macrophage polarisation.

4-hydroxy 2-nonenal ; Macrophages ; Osteoarthritis

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