Interaction of monocytes with glomerular mesangial cell matrix in the pathogenesis of glomerular injury

摘要: Acute inflammatory kidney diseases may resolve, leaving limited residual damage or progress to cause chronic renal scarring characterized by glomerulosclerosis and interstitial fibrosis. Understanding the mechanisms that control inflammation within the facilitate development of treatment strategies prevent irreversible kidney damage and slow progression disease. Infiltration of mononuclear cells is recognized as an early event in many different conditions may ultimately lead injury. Having extravasated from blood vessels at sites of injury, these multifunctional differentiate into tissue macrophages, which depending on their phenotype, have potential both promote resolution of inflammation scarring, making them attractive target for therapy. Having left glomerular capillary lumen, mononuclear are very likely encounter the mesangial matrix. It was therefore hypothesized interactions between monocytes and matrix components might modify behavior infiltrating thereby modify outcome process. The work presented this thesis demonstrates mesangial activates monocytes leading expression peroxisome proliferators activated receptor γ the CD36 scavenger receptor, markers macrophage differentiation. Since LDL accumulation mesangium contribute injury, interaction between lipoprotein also examined. These studies demonstrated that LDL becomes oxidized when exposed components, possibly due loss of protective antioxidants. The presence has induce cell chemokine production, which further monocyte influx glomerulus. Furthermore, matrix-activated monocytes internalized oxidized via CD36 foam formation, a recognized characteristic feature Foam formation turn amplify perpetuate disease process driving production cytokines and growth factors. Finally, establish observations were relevant human glomerular disease, macrophages expressing PPAR-γ scavenger receptor biopsy samples taken patients with inflammatory glomerular demonstrated, using sections non-inflamed kidneys as controls. imply monocyte-matrix important in the context represent a therapies designed limit injury resulting inflammation.