Urinary levels of chemokines (MCAF/MCP-1, IL-8) reflect distinct disease activities and phases of human IgA nephropathy.
Leukocytes have been implicated to be involved in the pathogenesis of IgA nephropathy (IgAN). To clarify the precise molecular mechanism of recruitment and activation of leukocytes in the subgroups of IgAN, latent, acute, and chronic types, we studied monocyte chemotactic and activating factor (MCAF/MCP-1) and interleukin (IL)-8 in urines and renal expression of these cytokines. Urinary MCAF levels were significantly higher in chronic type, and were correlated with pathological progressive factors such as mesangial proliferation and interstitial cellular infiltration associated with CD68-positive macrophage. On the other hand, urinary IL-8 elevated only in acute type and were correlated with glomerular endocapillary proliferation and the degree of hematuria. In immunohistochemical study, IL-8 was mainly observed in glomeruli, otherwise MCAF in vascular endothelial cells, tubular epithelial cells, and infiltrated mononuclear cells in the interstitial lesions. These observations demonstrated that MCAF and IL-8 were differentially expressed in kidneys with IgAN, and their subtypes, and suggest that chemokines may be involved in the pathogenesis of IgAN at distinct phases or pathological lesions, possibly through the recruitment and activation of a distinct type of leukocyte.
Yokoyama
H
H
First Department of Internal Medicine, School of Medicine, Kanazawa University, Japan. dialysis@med.kanazawa-u.ac.jp
Wada
T
T
Furuichi
K
K
Segawa
C
C
Shimizu
M
M
Kobayashi
K
K
Su
S
S
Mukaida
N
N
Matsushima
K
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D018932:Chemokine CCL2 / Q000378:metabolism / Q000652:urine*; D005260:Female; D005920:Glomerular Mesangium / Q000378:metabolism / Q000473:pathology; D005922:Glomerulonephritis, IGA / Q000473:pathology / Q000652:urine*; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000378:metabolism / Q000652:urine*; D007668:Kidney / Q000378:metabolism; D008297:Male; D008875:Middle Aged
D018932:Chemokine CCL2; D016209:Interleukin-8