The sialoadhesin (CD169) expressing a macrophage subset in human proliferative glomerulonephritis.
BACKGROUND
Sialoadhesin (Sn; CD169) is a lectin-like receptor whose expression is restricted to subsets of tissue and inflammatory macrophages. We have previously identified accumulation of Sn+ macrophages as an important marker of disease progression versus remission in rat mesangial proliferative nephritis. The current study examined the significance of Sn+ macrophages in human proliferative glomerulonephritis.


METHODS
Frozen kidney sections from normal adult human kidney (n = 4) and pediatric nephropathy (n = 40) were stained for total macrophages (CD68+ cells), Sn+ macrophages, CD3+ T-cells and collagen type I by immunofluorescence. Leukocyte infiltration and the severity of glomerular lesions and interstitial damage were scored. A second protocol biopsy was performed in 27 cases and clinical and biopsy-based data obtained.


RESULTS
Sn+ macrophages were absent from glomeruli in normal adult human kidney and in thin basement membrane disease (n = 4), but were detected in 4 of 9 cases of purpura nephritis; 7 of 17 IgA nephropathy; 5 of 5 membranoproliferative glomerulonephritis, and 5 of 5 lupus nephritis. Sn+ macrophages were localized in areas of focal glomerular and interstitial damage. Two-colour immunostaining confirmed that Sn+ cells are a subset of total CD68+ macrophages. The number of glomerular Sn+ macrophages correlated with the degree of proteinuria and glomerular lesions (r = 0.44, P = 0.0045 and r = 0.82, P<0.0001; respectively), while interstitial Sn+ macrophages correlated with the degree of proteinuria and interstitial damage (r = 0.59, P<0.0001 and r = 0.75, P<0.0001; respectively). Combined immunostaining revealed that interstitial Sn+ macrophages and CD3+ T-cells co-localized in areas of tubulointerstitial damage with increased type I collagen deposition. There was significant correlation between the number of interstitial Sn+ macrophages and CD3+ T-cells (r = 0.74, P<0.0001). Most patients responded to a 2 year period of glucocorticoid therapy with a reduction in proteinuria and glomerular lesions and this correlated with the reduction in the number of glomerular Sn+ macrophages.


CONCLUSIONS
This study has identified Sn+ cells as a macrophage subset whose accumulation in the kidney correlates with proteinuria and histologic damage. These results, together with recent findings from animal studies, suggest that Sn+ macrophages may play an important role in progressive renal disease.
Ikezumi
Yohei
Y
Division of Pediatrics, Niigata University Medical and Dental Hospital, Asahimachi-dori, Niigata 951-8510, Japan. ikezumi@med.niigata-u.ac.jp
Suzuki
Toshiaki
T
Hayafuji
Shinichi
S
Okubo
Soichiro
S
Nikolic-Paterson
David J
DJ
Kawachi
Hiroshi
H
Shimizu
Fujio
F
Uchiyama
Makoto
M
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism*; D001706:Biopsy; D002648:Child; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015432:Glomerulonephritis, Membranoproliferative / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D012720:Severity of Illness Index; D063267:Sialic Acid Binding Ig-like Lectin 1
D015703:Antigens, CD; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C571166:SIGLEC1 protein, human; D063267:Sialic Acid Binding Ig-like Lectin 1