Roles of the mesangium in glomerular function.

Among the multiple functions of the mesangial cell in glomerular physiology and pathophysiology, those of structural support of the capillary network, of participation in filtration regulation and in glomerular injury have attracted considerable interest. These roles are supported by studies with anti-Thy 1.1 antibody induced mesangiolysis in rats and by genetic knockout experiments of PDGF or PDGF-receptors in mice. These mice show a lack of mesangial cell development and a concomitant failure to establish a glomerular capillary network. Micropuncture experiments in the rats with mesangiolysis also provide support for a role of mesangial cells in the regulation of glomerular filtation. Numerous studies have established a contribution of mesangial cells to immunological and non-immunological injury in the glomerulus. Under many conditions this involves the recruitment and activation of macrophages, which require generation of chemotactic peptides and expression of adhesion molecules. Stimulation of mesangial cells with immune complexes and proinflammatory cytokines such as TNF-alpha or IL-1 results in the release of chemokines and in the appearance of adhesion molecules on the mesangial cells. The generation of reactive oxygen species appears to play a major role in this context and involves, at least in part, the activation of the transcription factor NF-kappa B. These results point toward mesangial cells as important participants in glomerular injury.