Monocyte chemoattractant protein 1 mediates glomerular macrophage infiltration in anti-GBM Ab GN.
Monocyte chemoattractant protein 1 (MCP-1) is a C-C chemokine with potent monocyte chemotactic and activating properties that may contribute to glomerular macrophage infiltration in anti-GBM Ab GN. We have previously reported increased glomerular steady state expression of MCP-1 mRNA relative to GAPDH mRNA in the heterologous phase of experimental anti-GBM Ab GN. In this report, we expand upon these data by demonstrating that the increase in MCP-1 mRNA correlated with MCP-1 protein expression at 24 hours that was determined with an ELISA (2069 +/- 147 pg/mg glom lysate). This increase in MCP-1 expression was associated with glomerular monocyte/ macrophage infiltration which peaked at 24 hours (8.2 +/- 1.0 ED-1 cells/glom). The site of MCP-1 mRNA production was localized by combining immunohistochemistry with in situ hybridization. The majority of cells which expressed MCP-1 mRNA at three hours were intrinsic glomerular cells, while 55% of the cells that expressed MCP-1 mRNA at 15 hours were monocytes/macrophages. To determine if MCP-1 affected glomerular macrophage infiltration, rats with alpha-GBM Ab GN were administered a polyclonal neutralizing Ab to rat MCP-1. This resulted in a 38% decline in glomerular macrophage infiltration (3.3 +/- 0.3 vs. 1.8 +/- 0.2 ED-1 cells/glom, P = 0.0001) that was associated with a 45% reduction in urinary protein excretion (260 +/- 53 vs. 162 +/- 46 mg/d, P = 0.0001). These data demonstrate an important role for MCP-1 in the pathogenesis of glomerular macrophage infiltration in anti-GBM Ab GN.
Tang
W W
WW
Department of Anatomic Pathology, Amgen Inc., Thousand Oaks, California, USA.
Qi
M
M
Warren
J S
JS
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D001485:Basement Membrane / Q000276:immunology; D018932:Chemokine CCL2 / Q000235:genetics / Q000502:physiology*; D002633:Chemotaxis / Q000502:physiology; D015870:Gene Expression; D005921:Glomerulonephritis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology*; D008264:Macrophages / Q000473:pathology* / Q000502:physiology*; D009500:Neutralization Tests; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011817:Rabbits; D051381:Rats; D011917:Rats, Inbred Lew
D000906:Antibodies; D018932:Chemokine CCL2; D012333:RNA, Messenger