Up‐regulation of ICAM‐1 and VCAM‐1 expression during macrophage recruitment in lipid induced glomerular injury in ExHC rats

Motoshi HATTORI, David J. NIKOLIC‐PATERSON, Hui Y. LAN, Hiroshi KAWAGUCHI, Katsumi ITO, Robert C. ATKINS

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19 Citations (Scopus)

Abstract

Summary: A number of studies have demonstrated an important role for macrophages (Mo) in lipid induced glomerular injury; however, little is known of the mechanisms which facilitate Mo infiltration in this disease. the present study examined the expression of adhesion molecules, intercellular adhesion molecule‐1 (ICAM‐1) and vascular cell adhesion molecule‐1 (VCAM‐1) during the development of glomerular Mo infiltration in ExHC rats; a strain which is susceptible to lipid induced glomerular injury. Twenty‐five male 6 week old ExHC rats were placed on a normal diet supplemented with 3% cholesterol, 0.6% sodium cholate and 15% olive oil (high‐cholesterol diet, HCD). Groups of five rats were killed prior to the beginning of the HCD or after 3 days, 1, 2 and 6 weeks on a HCD. A group of five matched ExHC rats on a normal diet served as a control. ExHC rats fed a HCD showed marked hypercholesterolaemia in the absence of any increase in plasma triglyceride levels from day 3 (190 ± 14 vs 42 ± 2 mg/dL in control; mean ± s.e.m., P<0.01), and developed mild proteinuria (21.9 ± 2.7 vs 5.2 ± 0.5 mg/24 h in control; P<0.01) and segmental glomerular lesions at week 6. Immunoperoxidase staining identified a significant increase in glomerular ED1 + Mo at week 1 (2.0 ± 0.2 vs 1.0 ± 0.1 ED1 + Mo/glomerular cross‐section in control, P<0.01) which was further increased at week 6 (6.9 ± 0.4 ED1 + Mo/gcs). There was also a significant increase in glomerular cells expressing the adhesion molecule ligands lymphocyte function‐associated antigen‐1 (LFA‐1) and very late antigen‐4 (VLA‐4). Coincident with Mo infiltration, there was an increase in the intensity of glomerular ICAM‐1 protein expression as shown by antibody staining. In addition, northern blot analysis of cortical RNA and in situ hybridization demonstrated an increase in glomerular ICAM‐1 and VCAM‐1 mRNA expression from day 3 onwards. In conclusion, these results suggest that both ICAM‐1/LFA‐1 and VCAM‐1/VLA‐4 interactions play an important role in Mo recruitment and accumulation during the development of lipid induced glomerular injury.

Original languageEnglish
Pages (from-to)221-232
Number of pages12
JournalNephrology
Volume1
Issue number3
DOIs
Publication statusPublished - 1 Jan 1995
Externally publishedYes

Keywords

  • ExHC rat
  • ICAM‐1
  • lipid induced glomerular injury
  • macrophage
  • VCAM‐1

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