Potential role for monocyte chemotactic protein-4 (MCP-4) in monocyte/macrophage recruitment in acute renal inflammation.
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.
Chakravorty
S J
SJ
Renal Immunobiology, MRC Centre for Immune Regulation, The Medical School, University of Birmingham, B15 2TT, UK.
Howie
A J
AJ
Girdlestone
J
J
Gentle
D
D
Savage
C O
CO
D000208:Acute Disease; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017252:CD3 Complex; D002478:Cells, Cultured; D005921:Glomerulonephritis / Q000276:immunology / Q000378:metabolism*; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000494:pharmacology; D007668:Kidney / Q000737:chemistry* / Q000276:immunology; D016030:Kidney Transplantation; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D018945:Monocyte Chemoattractant Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D054390:Receptors, CCR2; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D013268:Stimulation, Chemical; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017252:CD3 Complex; D007371:Interferon-gamma; D018945:Monocyte Chemoattractant Proteins; D054390:Receptors, CCR2; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; C099677:CCL13 protein, human; C515334:CCR2 protein, human; C515350:CCR3 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule