Chemokine and chemokine receptor expression during initiation and resolution of immune complex glomerulonephritis

J Am Soc Nephrol. 2001 May;12(5):919-931. doi: 10.1681/ASN.V125919.

Abstract

Chemokines participate in leukocyte infiltration, which plays a major role in glomerular injury during immune complex glomerulonephritis (IC-GN). Because target cell expression of chemokine receptors (CCR) is thought to mediate leukocyte migration, the expression pattern of chemokines and CCR in a model of IC-GN was examined. The transient course and predominant glomerular pathology of this model allows the examination of both the induction and resolution phases of IC-GN. GN was induced in mice by daily apoferritin injection for 2 wk. Urine samples and kidneys were obtained at 1, 2, and 4 wk. Albuminuria was noted at 2 wk, but resolved after 4 wk. This was associated with glomerular IC deposits and mesangial proliferation. Glomerular macrophage infiltration was prominent at 1 and 2 wk, which resolved at 4 wk. Expression of monocyte chemoattractant protein-1 (MCP-1) and RANTES mRNA was upregulated at week 1 and decreased to control levels at weeks 2 and 4. The expression was localized to glomeruli by in situ hybridization and immunohistochemistry. The mRNA of CCR1, CCR2, and CCR5 but not CCR3 or CCR4 were upregulated at week 1 and decreased at weeks 2 and 4. Expression of CCR5 was located to the glomerulus by in situ hybridization and quantitative reverse transcription-PCR of isolated glomeruli. In summary, in a model of transient IC-GN, MCP-1 and RANTES and their receptors CCR1, CCR2, and CCR5 are expressed early and are already downregulated at the peak of proteinuria and leukocyte infiltration. Resolution of glomerulonephritis is associated with a return to baseline of chemokine and CCR expression. Therefore, it is concluded that glomerular MCP-1 and RANTES production directs circulating leukocytes that express CCR1, CCR2, and CCR5 into the glomerulus. After initiating GN, MCP-1 and RANTES and their receptors are readily downregulated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoferritins / administration & dosage
  • Base Sequence
  • Chemokines / genetics*
  • Chemokines / metabolism*
  • DNA Primers / genetics
  • Female
  • Gene Expression
  • Glomerulonephritis / etiology
  • Glomerulonephritis / genetics*
  • Glomerulonephritis / immunology*
  • Glomerulonephritis / pathology
  • Immune Complex Diseases / etiology
  • Immune Complex Diseases / genetics*
  • Immune Complex Diseases / immunology*
  • Immune Complex Diseases / pathology
  • Immunohistochemistry
  • In Situ Hybridization
  • Leukocytes / pathology
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Electron
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Chemokine / genetics*
  • Receptors, Chemokine / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Chemokines
  • DNA Primers
  • RNA, Messenger
  • Receptors, Chemokine
  • Apoferritins