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 language | English |
|---|---|
| Pages (from-to) | S47-S50 |
| Number of pages | 4 |
| Journal | Kidney International |
| Volume | 56 |
| Issue number | 71 |
| DOIs | |
| Publication status | Published - 1 Dec 1999 |
Keywords
- Hypercholesterolemia
- Leukocyte adhesion molecule
- Lipids
- M-CSF
- MIF
Cite this
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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 journal › Article › Research › peer-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
KW - MIF
UR - http://www.scopus.com/inward/record.url?scp=0032973662&partnerID=8YFLogxK
U2 - 10.1046/j.1523-1755.1999.07112.x
DO - 10.1046/j.1523-1755.1999.07112.x
M3 - Article
VL - 56
SP - S47-S50
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 71
ER -