T. Oda et al., CLINICOPATHOLOGICAL SIGNIFICANCE OF INTRATUBULAR GIANT MACROPHAGES INPROGRESSIVE GLOMERULONEPHRITIS, Kidney international, 53(5), 1998, pp. 1190-1200
Very large macrophages, which we have termed ''giant macrophages'' (G-
M phi), have been found in renal tubules, some containing cytoplasmic
vacuoles. To elucidate their pathophysiological roles, we examined ren
al biopsy tissues from various primary glomerulonephritis (GN) and tub
ulointerstitial nephritis (TIN) using immuno-histochemistry; with mono
clonal antibodies against M phi and other cell surface markers. Giant
macrophages were absent or rare in TIN, minimal change nephrotic syndr
ome, and minor glomerular abnormalities, but G-M phi was plentiful in
progressive glomerulonephrides such as IgA nephropathy with crescents,
membranoproliferative GN, focal segmnental glomerulosclerosis, and es
pecially in crescentic GN. These G-M phi were usually seen in the lume
n of renal tubules, but occasionally were found in the Bowman's spaces
and glomerular tufts, and similar cells were also found in urine. Mor
eover, they frequently made contact with tubular epithelial cells expr
essing intercellular adhesion molecule-1, and the tubular epithelial c
ells in such lesions often had dt generative changes. Giant M phi may
damage tubular epithelial cells from the luminal side. Phenotypically,
G-M phi showed activated (CD71(+)) and mature (25F9(+)) characteristi
cs along with features of M phi (CD68(+)), and the cytoplasm contained
a great deal of lipids. The numbers of G-M phi, in renal tissues clos
ely correlated with the degree of hematuria (rho = 0.5, P < 0.001), se
rum creatinine value (r = 0,63, P < 0.001) in GN patients (N = 96) and
with proteinuria in IgA nephropathy patients (r = 0.89, P < 0.001, N
= 27). These data suggest that G-M phi are M phi that were activated a
nd matured in certain active inflammatory: sites. which flowed into tu
bules and then into urine. Thus, the existence of G-M phi in biopsy ti
ssue or urine reflect the activity of GN and may have a predictive val
ue for the progression of GN.