The mesangial phagocyte and its regulation of contractile cell biology

The mesangium constitutes the core of the renal glomerulus. It consists of the matrix, composed of mucopolysaccharides and glycoproteins, and two cell types. The predominant cell type is the mesangial cell, resembling a vascular smooth muscle cell. Up to 15% of the mesangial cell population additionally consists of resident mesangial phagocytes. These are derived from the bone marrow and belong to the family of mononuclear leukocytes. They are phagocytic, express Fc and C3 receptors, and display membrane Ia antigens. They syngeneically stimulate lymphocyte proliferation via antigen presentation. They are equally potent allogeneic stimulating cells in mixed lymphocyte culture. The mesangium is also the preferred locus of the induced migration of monocytes in inflammatory and proteinuric states. The presence of both normally resident and inflammation-associated mesangial phagocyte is lipid dependent. Hyperlipidemia increases the population of mesangial phagocytes. Lipid restriction decreases their number and, as a result, diminishes the allogenicity of renal transplants and blunts the progression of glomerulonephritis. One signal regulating the infiltration of the mesangium by mononuclear phagocytes appears to be a complex neutral lipid that is highly and specifically chemotactic for monocytes. It is released by the contractile mesangial cell in response to the stimulation of its Fc receptor and to the mesangial deposition of macromolecules. Both resident and inflammatory mesangial phagocytes secrete factors that remodel the mesangial matrix, stimulate mesangial cell proliferation, alter glomerular basement membrane permeability, and regulate blood flow. The persistence of mononuclear phagocytes in an activated state within the mesangium contributes to the marked alteration in mesangial structure that eventuates in glomerulosclerosis in both immune and nonimmune models of glomerular injury.