Distinct expression of CCR1 and CCR5 in glomerular and interstitial lesions of human glomerular diseases.
We investigated the presence of CCR1- and CCR5-positive cells immunohistochemically in the kidneys of 38 patients with several renal diseases, including 13 crescentic glomerulonephritis patients. In addition, we determined cell phenotypes of CCR1- and CCR5-positive cells using a dual immunostaining technique. Urinary levels of their ligands, for CCR1 and CCR5; macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and regulated upon activation in normal T cells expressed and secreted (RANTES) were evaluated by enzyme-linked immunosorbent assay. CCR1- and CCR5-positive cells were detected in both glomeruli and interstitium of the diseased kidneys. Using a dual immunostaining technique, these positive cells were CD68-positive macrophages (MPhi) and CD3-positive T cells. The number of CCR1-positive cells in glomeruli was correlated with urinary levels of MIP-1alpha. The number of CCR1-positive cells in the interstitium was correlated with both urinary MIP-1alpha and RANTES levels. CCR1-positive cells in the interstitium remained after glucocorticoid therapy, most of which were MPhi, and were correlated with the intensity of interstitial fibrosis and tubular atrophy. Glomerular CCR5-positive cells were well correlated with extracapillary lesions and urinary MIP-1alpha levels, while interstitial CCR5-positive cells, mainly CD3-positive T cells, were correlated with interstitial lesions and urinary RANTES levels. Renal CCR5-positive cells were dramatically decreased during convalescence induced by glucocorticoids. These results suggest that chemokine receptor signaling may be pivotal for human renal diseases through the recruitment and activation of MPhi and T cells; CCR5-positive cells may participate in glomerular lesions including extracapillary lesions via MIP-1alpha and in interstitial lesions via RANTES. CCR1 may be involved in interstitial lesions in resolving phase after glucocorticoid therapy.
Furuichi
K
K
First Department of Internal Medicine and Division of Blood Purification, School of Medicine, Kanazawa National Hospital, Kanazawa, Japan. kfuruich@medf.m.kanazawa-u.ac.jp
Wada
T
T
Sakai
N
N
Iwata
Y
Y
Yoshimoto
K
K
Shimizu
M
M
Kobayashi
K
K
Takasawa
K
K
Kida
H
H
Takeda
S I
SI
Mukaida
N
N
Matsushima
K
K
Yokoyama
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000502:physiology; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008181:Lupus Nephritis / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000502:physiology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D054389:Receptors, CCR1; D019713:Receptors, CCR5 / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism
C515300:CCR1 protein, human; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D005938:Glucocorticoids; D019402:Macrophage Inflammatory Proteins; D054389:Receptors, CCR1; D019713:Receptors, CCR5; D019707:Receptors, Chemokine