Oxidized low-density lipoprotein stimulates monocyte adhesion to glomerular endothelial cells

Vaijinath S. Kamanna; Pai Rama; Ha Hunjoo; Michael A. Kirschenbaum; Daeyoung D. Roh

doi:10.1046/j.1523-1755.1999.00470.x

Oxidized low-density lipoprotein stimulates monocyte adhesion to glomerular endothelial cells

Vaijinath S. Kamanna, Pai Rama, Ha Hunjoo, Michael A. Kirschenbaum, Daeyoung D. Roh

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

51 Scopus citations

Abstract

Background. Abnormalities in lipid and lipoprotein metabolism have been implicated in the pathogenesis of glomerulosclerosis. Atherogenic lipoproteins [for example, low-density lipoprotein (LDL) and oxidized LDL (ox-LDL)] have been shown to stimulate glomerular monocyte chemoattractants involved in monocyte infiltration. However, the role of LDL and ox-LDL in the early monocyte adhesion to glomerular endothelial cells (ECs) and associated intracellular signaling mechanisms are not clearly understood. Methods. In this study, we examined the effect of LDL and ox-LDL on intracellular signaling mechanisms associated with monocyte adhesion to glomerular ECs and intercellular adhesion molecule-1 (ICAM-1) expression. Results. Ox-LDL, but not LDL, stimulated EC ICAM-1 expression and monocyte adhesion. Ox-LDL elevated protein tyrosine kinase (PTK) activity, and the preincubation of ECs with specific PTK inhibitors blocked ox-LDL-induced ICAM-1 message and monocyte adhesion. Whereas experimental maneuvers that inhibit either protein kinase C activation (by PKC depletion or with inhibitors) or G(j)-protein- mediated pathways (pertussis toxin sensitive) had no effect on ox-LDL- induced monocyte adhesion and ICAM-1 expression, cAMP-elevating compounds did not induce ICAM-1 or monocyte adhesion. Conclusions. The data indicate that ox-LDL, by stimulating monocyte adhesion to the glomerular endothelium, may regulate monocyte infiltration within the glomerulus, supporting an early pathobiological role for atherogenic lipoproteins in glomerular injury. The results suggest that the activation of specific PTK and associated signaling may, at least in part, play a critical role in ox-LDL-mediated endothelial- monocyte interaction-related events. The data suggest that the interventions aimed at modifying associated intracellular signaling events within the glomerulus may provide potential therapeutic modalities in monocyte/macrophage-mediated glomerular disease.

Original language	English
Pages (from-to)	2192-2202
Number of pages	11
Journal	Kidney International
Volume	55
Issue number	6
DOIs	https://doi.org/10.1046/j.1523-1755.1999.00470.x
State	Published - 1999

Bibliographical note

Funding Information:
This study was supported by a Merit Review from the Department of Veterans Affairs and an Institutional Fellowship from the National Kidney Foundation of Southern California. We wish to thank Dr. Gary E. Striker (National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, MD, USA) for providing murine glomerular ECs. We thank Dr. Babu V. Bassa for assistance in lipoprotein preparation and tyrosine kinase assays.

Keywords

Cell signaling
Glomerulosclerosis
Intracellular signaling
Lipid metabolism
Lipoprotein

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10.1046/j.1523-1755.1999.00470.x

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@article{b68638ad60b14a28a8d235eba6b7528d,

title = "Oxidized low-density lipoprotein stimulates monocyte adhesion to glomerular endothelial cells",

abstract = "Background. Abnormalities in lipid and lipoprotein metabolism have been implicated in the pathogenesis of glomerulosclerosis. Atherogenic lipoproteins [for example, low-density lipoprotein (LDL) and oxidized LDL (ox-LDL)] have been shown to stimulate glomerular monocyte chemoattractants involved in monocyte infiltration. However, the role of LDL and ox-LDL in the early monocyte adhesion to glomerular endothelial cells (ECs) and associated intracellular signaling mechanisms are not clearly understood. Methods. In this study, we examined the effect of LDL and ox-LDL on intracellular signaling mechanisms associated with monocyte adhesion to glomerular ECs and intercellular adhesion molecule-1 (ICAM-1) expression. Results. Ox-LDL, but not LDL, stimulated EC ICAM-1 expression and monocyte adhesion. Ox-LDL elevated protein tyrosine kinase (PTK) activity, and the preincubation of ECs with specific PTK inhibitors blocked ox-LDL-induced ICAM-1 message and monocyte adhesion. Whereas experimental maneuvers that inhibit either protein kinase C activation (by PKC depletion or with inhibitors) or G(j)-protein- mediated pathways (pertussis toxin sensitive) had no effect on ox-LDL- induced monocyte adhesion and ICAM-1 expression, cAMP-elevating compounds did not induce ICAM-1 or monocyte adhesion. Conclusions. The data indicate that ox-LDL, by stimulating monocyte adhesion to the glomerular endothelium, may regulate monocyte infiltration within the glomerulus, supporting an early pathobiological role for atherogenic lipoproteins in glomerular injury. The results suggest that the activation of specific PTK and associated signaling may, at least in part, play a critical role in ox-LDL-mediated endothelial- monocyte interaction-related events. The data suggest that the interventions aimed at modifying associated intracellular signaling events within the glomerulus may provide potential therapeutic modalities in monocyte/macrophage-mediated glomerular disease.",

keywords = "Cell signaling, Glomerulosclerosis, Intracellular signaling, Lipid metabolism, Lipoprotein",

author = "Kamanna, {Vaijinath S.} and Pai Rama and Ha Hunjoo and Kirschenbaum, {Michael A.} and Roh, {Daeyoung D.}",

note = "Funding Information: This study was supported by a Merit Review from the Department of Veterans Affairs and an Institutional Fellowship from the National Kidney Foundation of Southern California. We wish to thank Dr. Gary E. Striker (National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, MD, USA) for providing murine glomerular ECs. We thank Dr. Babu V. Bassa for assistance in lipoprotein preparation and tyrosine kinase assays.",

year = "1999",

doi = "10.1046/j.1523-1755.1999.00470.x",

language = "English",

volume = "55",

pages = "2192--2202",

journal = "Kidney International",

issn = "0085-2538",

publisher = "Elsevier B.V.",

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}

TY - JOUR

T1 - Oxidized low-density lipoprotein stimulates monocyte adhesion to glomerular endothelial cells

AU - Kamanna, Vaijinath S.

AU - Rama, Pai

AU - Hunjoo, Ha

AU - Kirschenbaum, Michael A.

AU - Roh, Daeyoung D.

N1 - Funding Information: This study was supported by a Merit Review from the Department of Veterans Affairs and an Institutional Fellowship from the National Kidney Foundation of Southern California. We wish to thank Dr. Gary E. Striker (National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, MD, USA) for providing murine glomerular ECs. We thank Dr. Babu V. Bassa for assistance in lipoprotein preparation and tyrosine kinase assays.

PY - 1999

Y1 - 1999

N2 - Background. Abnormalities in lipid and lipoprotein metabolism have been implicated in the pathogenesis of glomerulosclerosis. Atherogenic lipoproteins [for example, low-density lipoprotein (LDL) and oxidized LDL (ox-LDL)] have been shown to stimulate glomerular monocyte chemoattractants involved in monocyte infiltration. However, the role of LDL and ox-LDL in the early monocyte adhesion to glomerular endothelial cells (ECs) and associated intracellular signaling mechanisms are not clearly understood. Methods. In this study, we examined the effect of LDL and ox-LDL on intracellular signaling mechanisms associated with monocyte adhesion to glomerular ECs and intercellular adhesion molecule-1 (ICAM-1) expression. Results. Ox-LDL, but not LDL, stimulated EC ICAM-1 expression and monocyte adhesion. Ox-LDL elevated protein tyrosine kinase (PTK) activity, and the preincubation of ECs with specific PTK inhibitors blocked ox-LDL-induced ICAM-1 message and monocyte adhesion. Whereas experimental maneuvers that inhibit either protein kinase C activation (by PKC depletion or with inhibitors) or G(j)-protein- mediated pathways (pertussis toxin sensitive) had no effect on ox-LDL- induced monocyte adhesion and ICAM-1 expression, cAMP-elevating compounds did not induce ICAM-1 or monocyte adhesion. Conclusions. The data indicate that ox-LDL, by stimulating monocyte adhesion to the glomerular endothelium, may regulate monocyte infiltration within the glomerulus, supporting an early pathobiological role for atherogenic lipoproteins in glomerular injury. The results suggest that the activation of specific PTK and associated signaling may, at least in part, play a critical role in ox-LDL-mediated endothelial- monocyte interaction-related events. The data suggest that the interventions aimed at modifying associated intracellular signaling events within the glomerulus may provide potential therapeutic modalities in monocyte/macrophage-mediated glomerular disease.

AB - Background. Abnormalities in lipid and lipoprotein metabolism have been implicated in the pathogenesis of glomerulosclerosis. Atherogenic lipoproteins [for example, low-density lipoprotein (LDL) and oxidized LDL (ox-LDL)] have been shown to stimulate glomerular monocyte chemoattractants involved in monocyte infiltration. However, the role of LDL and ox-LDL in the early monocyte adhesion to glomerular endothelial cells (ECs) and associated intracellular signaling mechanisms are not clearly understood. Methods. In this study, we examined the effect of LDL and ox-LDL on intracellular signaling mechanisms associated with monocyte adhesion to glomerular ECs and intercellular adhesion molecule-1 (ICAM-1) expression. Results. Ox-LDL, but not LDL, stimulated EC ICAM-1 expression and monocyte adhesion. Ox-LDL elevated protein tyrosine kinase (PTK) activity, and the preincubation of ECs with specific PTK inhibitors blocked ox-LDL-induced ICAM-1 message and monocyte adhesion. Whereas experimental maneuvers that inhibit either protein kinase C activation (by PKC depletion or with inhibitors) or G(j)-protein- mediated pathways (pertussis toxin sensitive) had no effect on ox-LDL- induced monocyte adhesion and ICAM-1 expression, cAMP-elevating compounds did not induce ICAM-1 or monocyte adhesion. Conclusions. The data indicate that ox-LDL, by stimulating monocyte adhesion to the glomerular endothelium, may regulate monocyte infiltration within the glomerulus, supporting an early pathobiological role for atherogenic lipoproteins in glomerular injury. The results suggest that the activation of specific PTK and associated signaling may, at least in part, play a critical role in ox-LDL-mediated endothelial- monocyte interaction-related events. The data suggest that the interventions aimed at modifying associated intracellular signaling events within the glomerulus may provide potential therapeutic modalities in monocyte/macrophage-mediated glomerular disease.

KW - Cell signaling

KW - Glomerulosclerosis

KW - Intracellular signaling

KW - Lipid metabolism

KW - Lipoprotein

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U2 - 10.1046/j.1523-1755.1999.00470.x

DO - 10.1046/j.1523-1755.1999.00470.x

M3 - Article

C2 - 10354268

AN - SCOPUS:0033031770

SN - 0085-2538

VL - 55

SP - 2192

EP - 2202

JO - Kidney International

JF - Kidney International

IS - 6

ER -

Oxidized low-density lipoprotein stimulates monocyte adhesion to glomerular endothelial cells

Abstract

Bibliographical note

Keywords

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