Role of marrow-derived monocytes and mesangial cells in removal of immune complexes from renal glomeruli.

Abstract

Intravenously administered antigen-antibody complexes or protein aggregates localize in the glomerular mesangium. The mechanism of removal of these deposited substances has been difficult to study. Based on observations that particulates such as ferritin (1) and silver-protein aggregates (2) were found within lyososomes, mesangial cells were concluded to be phagocytic and therefore to participate in the clearing of immune complexes and aggregated IgG from the mesangium. In studies with injection of preformed immune complexes, some of the complexes deposited in glomeruli appeared to be taken up by monocytes rather than mesangial cells (3, 4). Resolution of this issue is clouded by the fact that differentiation between resident and infiltrating cells on purely morphologic grounds is not possible for the majority of cells in the mesangium. The observation that peripheral monocytes are capable of division in local sites of inflammation (5, 6) suggests that studies utilizing labeled bone marrow cells or cross-transplantation of kidneys shortly after pulse labeling may be difficult to interpret.For these reasons, we chose to study the Chediak-Higashi (CH)1 mouse; and thereby take advantage of their characteristic giant lysosomes as a marker which is visible by both light and electron microscopy.In this study we found that CH mice cleared immune complexes normally and their mesangial cells did not contain large lysosomes in the resting state. By examining glomeruli in marrow cross-transplanted CH and C57BL/6J mice we found that after induction of glomerulonephritis with preformed immune complex administration, many of the cells in the glomeruli were marrow derived. The same marrow derived cells contained morphologically defined immune complexes, whereas resident mesangial cells did not. We therefore conclude that mesangial cells do not make a significant contribution to the phagocytic removal of immune complexes from the mesangial matrix. Materials and MethodsMarrow Transplantation. Normal C57BL/6J and the syngeneic CH (beige C57BL/6(bg/bg)) mice were obtained from the breeding colony maintained at the University of Washington by Doctors N. Wolf and E. Chi. 2-too-old female and male mice were used for marrow transplantation or administration of immune complexes.

The C1q binding assay in systemic lupus erythematosus

“…Both vascular volume (23) and preexisting glomerular damage (24) may be determinants of IC uptake. Intrarenal deposition of localized IC appears to be a function of the phagocytic mononuclear cells in the mesangium (25).…”

Mononuclear cells in glomeruli and cytokines in urine reflect the severity of experimental proliferative immune complex glomerulonephritis

“…Complement-generated chemotactins and/or Fc receptor interactions with glomerular deposits of immunoglobulins may be involved (Striker, Mannik & Tung, 1979;Holdsworth, 1983). The local expression of cell-mediated immunily has also been implicated in the perpetuation of glomerular inflammation in proliferative immune complex glomeruionephritis (Bhan et al, 1980).…”

The Aging Kidney Phenotype and Systemically Derived Stem Cells

“…3,25 Whether phagocytosis of antigen-antibody complexes was induced in mesangial cells was examined in Chediak-Higashi mice, using BMT. This study found that the complexes were principally taken up by cells containing giant lysozomes, 26 suggesting that macrophages derived from the Chediak-Higashi bone marrow donor were the principal phagocytic cells in the mesangial region.…”