O 5 . 6 Oxidative damage of PG ’ s core proteins during hyperthyroid pathology

Human blood mononuclear cells, like monocytes, migrate into connective tissues during early steps of inflammation and locally interact with extracellular matrix macromolecules or their fragments (matrikines). These interactions, lead to differentiation of the monocytes either to macrophages (MF) or to dendritic cells (DC). Extracellular matrix compounds are able to modulate the mononuclear cell behaviour. For example, interactions with collagen via integrins initiate the cascade of early inflammation events. In skin, resident DC, the Langerhans cells, under stimulation with pathogen, acquire a migratory phenotype. After loading with antigen DC can be further transformed into mature cells. In addition to cell surface receptors directly engaged in antigen capture and transformation, mononuclear cells express a complex spectrum of cell surface proteoglycans. Resident, immature DC express a most complex spectrum of glypicans and syndecans. Migratory, mature DC express glypican-3, not present in others cell subsets. Immature DC possess the highest metabolic activity and the monocytes the lowest metabolic activity for the synthesis of cell surface proteoglycans in comparison with mature DC and MF. The enhanced synthesis of proteoglycans by immature dendritic cells corroborate with their role in tissue homeostasis. Migration of mononuclear cells through extracellular matrix is directed by the expression of matrix metalloproteinases including MMP-9 but also by tissue inhibitor of metalloproteinases-1. Macrophage inflammatory protein-3β increases mature DC migration by up-regulation the plasma membrane-associated MMP-9 active form. Remodelling of the monocyte lineage cells during interaction with extracellular matrix contributes to their immunological properties and constitute a tool to modulate their behaviour for cell therapy purpose.