Mechanisms of glomerular macrophage infiltration in lipid-induced renal injury

Motoshi Hattori, David J. Nikolic-Paterson, Kenichi Miyazaki, Nicole M. Isbel, Hui Y. Lan, Robert C. Atkins, Hiroshi Kawaguchi, Katsumi Ito

Research output: Contribution to journalArticleResearchpeer-review

54 Citations (Scopus)

Abstract

Background. A number of studies have demonstrated an important role for macrophages (Mφ) in lipid-induced glomerular injury; however, little is known of the mechanisms that facilitate Mφ infiltration in this disease. This study examined the expression of Mφ chemotactic molecules Mφ colony-stimulating factor (M-CSF) and Mφ migration inhibitory factor (MIF) and leukocyte adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) during the induction of glomerular Mφ infiltration in ExHC rats, a strain that is susceptible to lipid-induced glomerular injury. Methods. Groups of five ExHC rats were fed a high-cholesterol diet (HCD) containing 3% cholesterol, 0.6% sodium cholate, and 15% olive oil and were killed after three days or one, two, or six weeks. Control animals were killed on day 0 or after six weeks on a normal diet. Results. ExHC rats fed an HCD showed marked hypercholesterolemia in the absence of any increase in plasma triglyceride levels from day 3 and developed mild proteinuria and segmental glomerular lesions at week 6. Immunoperoxidase staining identified a significant increase in glomerular ED1+ Mφ at week 1, which was further increased at week 6, when Mφ-derived foam cells were seen in almost all glomeruli. Many of the infiltrating glomerular Mφ expressed lymphocyte function-associated antigen-1 (LFA-1) and very late antigen-4 (VLA-4), which are ligands for ICAM-1 and VCAM-1, respectively. Coincident with the induction of hypercholesterolemia on day 3 and prior to significant Mφ infiltration, combined in situ hybridization and immunohistochemistry staining demonstrated a marked up-regulation of M-CSF and MIF mRNA expression by glomerular mesangial cells and podocytes. There was also a significant increase in ICAM-1 and VCAM-1 mRNA expression by intrinsic glomerular cells, including endothelial cells, on day 3 of the HCD. Conclusion. These results suggest that hypercholesterolemia can induce a classic proinflammatory response within the kidney glomerulus, involving production of well-described Mφ chemotactic and adhesion molecules, which results in Mφ recruitment and the development of glomerular injury.

Original languageEnglish
Pages (from-to)S47-S50
Number of pages4
JournalKidney International
Volume56
Issue number71
DOIs
Publication statusPublished - 1 Dec 1999

Keywords

  • Hypercholesterolemia
  • Leukocyte adhesion molecule
  • Lipids
  • M-CSF
  • MIF

Cite this

Hattori, Motoshi ; Nikolic-Paterson, David J. ; Miyazaki, Kenichi ; Isbel, Nicole M. ; Lan, Hui Y. ; Atkins, Robert C. ; Kawaguchi, Hiroshi ; Ito, Katsumi. / Mechanisms of glomerular macrophage infiltration in lipid-induced renal injury. In: Kidney International. 1999 ; Vol. 56, No. 71. pp. S47-S50.
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abstract = "Background. A number of studies have demonstrated an important role for macrophages (Mφ) in lipid-induced glomerular injury; however, little is known of the mechanisms that facilitate Mφ infiltration in this disease. This study examined the expression of Mφ chemotactic molecules Mφ colony-stimulating factor (M-CSF) and Mφ migration inhibitory factor (MIF) and leukocyte adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) during the induction of glomerular Mφ infiltration in ExHC rats, a strain that is susceptible to lipid-induced glomerular injury. Methods. Groups of five ExHC rats were fed a high-cholesterol diet (HCD) containing 3{\%} cholesterol, 0.6{\%} sodium cholate, and 15{\%} olive oil and were killed after three days or one, two, or six weeks. Control animals were killed on day 0 or after six weeks on a normal diet. Results. ExHC rats fed an HCD showed marked hypercholesterolemia in the absence of any increase in plasma triglyceride levels from day 3 and developed mild proteinuria and segmental glomerular lesions at week 6. Immunoperoxidase staining identified a significant increase in glomerular ED1+ Mφ at week 1, which was further increased at week 6, when Mφ-derived foam cells were seen in almost all glomeruli. Many of the infiltrating glomerular Mφ expressed lymphocyte function-associated antigen-1 (LFA-1) and very late antigen-4 (VLA-4), which are ligands for ICAM-1 and VCAM-1, respectively. Coincident with the induction of hypercholesterolemia on day 3 and prior to significant Mφ infiltration, combined in situ hybridization and immunohistochemistry staining demonstrated a marked up-regulation of M-CSF and MIF mRNA expression by glomerular mesangial cells and podocytes. There was also a significant increase in ICAM-1 and VCAM-1 mRNA expression by intrinsic glomerular cells, including endothelial cells, on day 3 of the HCD. Conclusion. These results suggest that hypercholesterolemia can induce a classic proinflammatory response within the kidney glomerulus, involving production of well-described Mφ chemotactic and adhesion molecules, which results in Mφ recruitment and the development of glomerular injury.",
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Mechanisms of glomerular macrophage infiltration in lipid-induced renal injury. / Hattori, Motoshi; Nikolic-Paterson, David J.; Miyazaki, Kenichi; Isbel, Nicole M.; Lan, Hui Y.; Atkins, Robert C.; Kawaguchi, Hiroshi; Ito, Katsumi.

In: Kidney International, Vol. 56, No. 71, 01.12.1999, p. S47-S50.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Mechanisms of glomerular macrophage infiltration in lipid-induced renal injury

AU - Hattori, Motoshi

AU - Nikolic-Paterson, David J.

AU - Miyazaki, Kenichi

AU - Isbel, Nicole M.

AU - Lan, Hui Y.

AU - Atkins, Robert C.

AU - Kawaguchi, Hiroshi

AU - Ito, Katsumi

PY - 1999/12/1

Y1 - 1999/12/1

N2 - Background. A number of studies have demonstrated an important role for macrophages (Mφ) in lipid-induced glomerular injury; however, little is known of the mechanisms that facilitate Mφ infiltration in this disease. This study examined the expression of Mφ chemotactic molecules Mφ colony-stimulating factor (M-CSF) and Mφ migration inhibitory factor (MIF) and leukocyte adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) during the induction of glomerular Mφ infiltration in ExHC rats, a strain that is susceptible to lipid-induced glomerular injury. Methods. Groups of five ExHC rats were fed a high-cholesterol diet (HCD) containing 3% cholesterol, 0.6% sodium cholate, and 15% olive oil and were killed after three days or one, two, or six weeks. Control animals were killed on day 0 or after six weeks on a normal diet. Results. ExHC rats fed an HCD showed marked hypercholesterolemia in the absence of any increase in plasma triglyceride levels from day 3 and developed mild proteinuria and segmental glomerular lesions at week 6. Immunoperoxidase staining identified a significant increase in glomerular ED1+ Mφ at week 1, which was further increased at week 6, when Mφ-derived foam cells were seen in almost all glomeruli. Many of the infiltrating glomerular Mφ expressed lymphocyte function-associated antigen-1 (LFA-1) and very late antigen-4 (VLA-4), which are ligands for ICAM-1 and VCAM-1, respectively. Coincident with the induction of hypercholesterolemia on day 3 and prior to significant Mφ infiltration, combined in situ hybridization and immunohistochemistry staining demonstrated a marked up-regulation of M-CSF and MIF mRNA expression by glomerular mesangial cells and podocytes. There was also a significant increase in ICAM-1 and VCAM-1 mRNA expression by intrinsic glomerular cells, including endothelial cells, on day 3 of the HCD. Conclusion. These results suggest that hypercholesterolemia can induce a classic proinflammatory response within the kidney glomerulus, involving production of well-described Mφ chemotactic and adhesion molecules, which results in Mφ recruitment and the development of glomerular injury.

AB - Background. A number of studies have demonstrated an important role for macrophages (Mφ) in lipid-induced glomerular injury; however, little is known of the mechanisms that facilitate Mφ infiltration in this disease. This study examined the expression of Mφ chemotactic molecules Mφ colony-stimulating factor (M-CSF) and Mφ migration inhibitory factor (MIF) and leukocyte adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) during the induction of glomerular Mφ infiltration in ExHC rats, a strain that is susceptible to lipid-induced glomerular injury. Methods. Groups of five ExHC rats were fed a high-cholesterol diet (HCD) containing 3% cholesterol, 0.6% sodium cholate, and 15% olive oil and were killed after three days or one, two, or six weeks. Control animals were killed on day 0 or after six weeks on a normal diet. Results. ExHC rats fed an HCD showed marked hypercholesterolemia in the absence of any increase in plasma triglyceride levels from day 3 and developed mild proteinuria and segmental glomerular lesions at week 6. Immunoperoxidase staining identified a significant increase in glomerular ED1+ Mφ at week 1, which was further increased at week 6, when Mφ-derived foam cells were seen in almost all glomeruli. Many of the infiltrating glomerular Mφ expressed lymphocyte function-associated antigen-1 (LFA-1) and very late antigen-4 (VLA-4), which are ligands for ICAM-1 and VCAM-1, respectively. Coincident with the induction of hypercholesterolemia on day 3 and prior to significant Mφ infiltration, combined in situ hybridization and immunohistochemistry staining demonstrated a marked up-regulation of M-CSF and MIF mRNA expression by glomerular mesangial cells and podocytes. There was also a significant increase in ICAM-1 and VCAM-1 mRNA expression by intrinsic glomerular cells, including endothelial cells, on day 3 of the HCD. Conclusion. These results suggest that hypercholesterolemia can induce a classic proinflammatory response within the kidney glomerulus, involving production of well-described Mφ chemotactic and adhesion molecules, which results in Mφ recruitment and the development of glomerular injury.

KW - Hypercholesterolemia

KW - Leukocyte adhesion molecule

KW - Lipids

KW - M-CSF

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