In situ analysis of C-C chemokine mRNA in human glomerulonephritis.
BACKGROUND
Glomerular and tubulointerstitial accumulations of macrophages and T cells are a prominent feature of immune inflammatory glomerulonephritis. The C-C family of chemokines are major mononuclear-cell chemoattractants and may be central to the recruitment of these cells.


METHODS
Using in situ hybridization (ISH) we analyzed the expression of mRNA for the C-C chemokines monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha and beta (MIP-1alpha, MIP-1beta) and RANTES in renal biopsy material from twenty patients with glomerulonephritis.


RESULTS
In overt inflammatory glomerulonephritides, chemokine transcripts were differentially expressed by glomerular and tubulointerstitial leukocyte infiltrates, glomerular parietal and proximal tubular epithelial cells and endothelial cells. There was little expression in minimal change nephropathy and normal tissue. Expression of individual chemokines correlated with intrarenal T cell and macrophage infiltrates. Combined immunohistochemistry and ISH demonstrated that 56.9% of cells expressing MCP-1 mRNA were CD68+ve (monocytes/macrophages) and 53% of infiltrating CD68 +ve cells were MCP-1 mRNA positive.


CONCLUSIONS
These studies indicate that the in situ production of C-C chemokines by resident and infiltrating cells may play a crucial role in regulating macrophage and T-cell recruitment in glomerulonephritis.
Cockwell
P
P
CCRIS and Department of Pathology, Medical School, University of Birmingham, Edgbaston, England, United Kingdom.
Howie
A J
AJ
Adu
D
D
Savage
C O
CO
D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D018932:Chemokine CCL2 / Q000235:genetics; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000235:genetics; D019742:Chemokines, CC / Q000235:genetics*; D005260:Female; D005921:Glomerulonephritis / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D019402:Macrophage Inflammatory Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis*; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017252:CD3 Complex; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; C067980:CD68 antigen, human; D000097382:CD68 Molecule