TY - JOUR
T1 - Potential role for monocyte chemotactic protein-4 (MCP-4) in monocyte/macrophage recruitment in acute renal inflammation
AU - Chakravorty, Srabasti
AU - Howie, Alexander
AU - Girdlestone, John
AU - Gentle, Dean
AU - Savage, Caroline
PY - 2001/6/1
Y1 - 2001/6/1
N2 - The CC chemokine, monocyte chemoattractant protein-4 (MCP-4), is an important chemoattractant for monocytes and T cells. Recent data indicate a role in renal inflammation. This study has used in situ hybridization and immunohistochemical analysis of cryostat sections of biopsy material taken from patients with acute renal allograft rejection and vasculitic glomerulonephritis to demonstrate renal expression of MCP-4, both at message and protein level. MCP-4 was primarily expressed at peritubular, periglomerular, and perivascular sites, irrespective of the inflammatory condition, and was associated with infiltrating CD3-positive lymphocytes and CD68-positive monocyte/macrophages. In addition, proximal tubular epithelial cells grown in culture from cortical fragments of human kidney showed low levels of constitutive MCP-4 expression, detectable by western blotting; this expression of MCP-4 was up-regulated in response to the pro-inflammatory cytokines, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). CCR3-, CCR5- and CCR2-expressing leukocyte populations were identified at sites of MCP-4 expression. Double-staining techniques revealed that CC chemokine receptor-expressing cells were primarily CD68-positive. These studies suggest an important role for MCP-4 in the recruitment and retention of monocytes/macrophages in renal inflammation.
AB - The CC chemokine, monocyte chemoattractant protein-4 (MCP-4), is an important chemoattractant for monocytes and T cells. Recent data indicate a role in renal inflammation. This study has used in situ hybridization and immunohistochemical analysis of cryostat sections of biopsy material taken from patients with acute renal allograft rejection and vasculitic glomerulonephritis to demonstrate renal expression of MCP-4, both at message and protein level. MCP-4 was primarily expressed at peritubular, periglomerular, and perivascular sites, irrespective of the inflammatory condition, and was associated with infiltrating CD3-positive lymphocytes and CD68-positive monocyte/macrophages. In addition, proximal tubular epithelial cells grown in culture from cortical fragments of human kidney showed low levels of constitutive MCP-4 expression, detectable by western blotting; this expression of MCP-4 was up-regulated in response to the pro-inflammatory cytokines, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). CCR3-, CCR5- and CCR2-expressing leukocyte populations were identified at sites of MCP-4 expression. Double-staining techniques revealed that CC chemokine receptor-expressing cells were primarily CD68-positive. These studies suggest an important role for MCP-4 in the recruitment and retention of monocytes/macrophages in renal inflammation.
KW - CC chemokine receptors
KW - MCP-4
KW - glomerulonephritis
KW - human kidney
KW - allograft rejection
UR - http://www.scopus.com/inward/record.url?scp=0034983825&partnerID=8YFLogxK
U2 - 10.1002/path.877
DO - 10.1002/path.877
M3 - Article
C2 - 11400154
SN - 1096-9896
VL - 194
SP - 239
EP - 246
JO - Journal of Pathology
JF - Journal of Pathology
IS - 2
ER -