Species-specific properties of the glomerular mesangium

Abstract

Mesangial cells play a central role in the physiology and pathophysiology of the glomerulus. To date, most of the in vitro studies have been performed in cultured rat mesangial cells, with only 10% of them performed in human mesangial cells. In this article, the major differences between results obtained with these two types of cultured cells will be reviewed. In rats and in humans, most of the mesangial cells appear to be of smooth muscle origin. In the rat, some of the cultured cells also express a phenotype suggesting a monocyte/macrophage origin. Phagocytosis and synthesis of cytokines or proinflammatory proteins that have been described in cultured rat cells seem mostly linked to this monocyte/ macrophage subtype of resident mesangial cells. In humans, macrophages are only detected in pathologic conditions, suggesting that they are not resident but rather infiltrating cells. Mesangial receptors, most notably angiotensin II receptors, are clearly present on mesangial cell membranes and are linked to prostaglandin E2 synthesis and to cell contraction. In humans, spontaneous prostanoid synthesis is low and is increased by the induction of cyclooxygenase by sodium butyrate in the medium. Even so, the amount of prostaglandin E2 synthesized by human mesangial cells is quantitatively low comparatively with that in rats. In rats, accordingly, mesangial cells play a role in the regulation of single-nephron GFR. In humans, angiotensin II also exerts a control on GFR but it is more difficult to demonstrate its contractile effect on human than on rat mesangial cells. The synthesis of inflammatory proteins has been detected in cultured rat mesangial cells, for example, tumor necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor. In contrast, tumor necrosis factor-alpha synthesis is undetectable in human mesangial cells. Moreover, phagocytosis linked to the generation of reactive oxygen species is not as clearly demonstrated in humans than as in rat. Finally, rat but not human mesangial cells were found to synthesize urokinase and to participate in remodeling of extracellular matrix. Many reasons may explain these discrepancies: species variations, conditions of culture, and variability of the culture medium, which may contain different concentrations of nonstandardized fetal calf serum. It remains to be ascertained whether the differences between rat and human mesangial cells are only in vitro findings related to culture conditions or whether they are indeed physiologically relevant.