Induction of macrophage migration through lactose‐insensitive receptor by elastin‐derived nonapeptides and their analog

Maeda, Isamu; Mizoiri, Noriaki; Briones, Maria Portia P.; Okamoto, Kouji

doi:10.1002/psc.845

Cited by 33 publications

(25 citation statements)

References 28 publications

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“…14 Intimal macrophages, involved in the pathogenesis of atherosclerosis, form foam cells and are CD11c positive but 5-LO negative. 14 Macrophages are attracted to the aortic wall by elastin degradation products 15 ; CC chemokines (monocyte chemoattractant protein-1 ͓MCP-1͔ and RANTES͓regulated on activation, normal T cell expressed and secreted͔) 16 -18 ; and granulocyte macrophage colony stimulating factor. 19 MCP-1 and RANTES are CC chemokines which have been found to increase during experimental development of AAA, using the elastase model.…”

Section: Macrophagesmentioning

confidence: 99%

Immune Cells and Molecular Mediators in the Pathogenesis of the Abdominal Aortic Aneurysm

Rizas

Ippagunta²,

Tilson³

2009

Cardiology in Review

134

105

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Abdominal aortic aneurysm is a multifactorial disease with genetic risk factors and an immunologic component. Immune cells, including macrophages, neutrophils, mast cells, B- and T- lymphocytes, along with vascular smooth muscle cells and adventitial fibroblasts, produce cytokines and enzymes, promoting an inflammatory reaction, extracellular matrix degradation, and neovascularization. Among the different enzymes secreted by immune and stromal cells, matrix metalloproteinase (MMP)-2, MMP-9, MMP-12, cathepsins, and neutrophil elastase cause medial degeneration. Chymase causes smooth muscle cell apoptosis, and MMP-3, MMP-8, and MMP-13 cause adventitial collagen degradation, promoting abdominal aortic aneurysm rupture. At the same time chemokines (interleukin 8, macrophage inflammatory protein 1 alpha, monocyte chemotactic protein-1) cause recruitment and proliferation of inflammatory cells, whereas cytokines (vascular endothelial growth factor and transforming growth factor-beta) promote neoangiogenesis.

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Section: Macrophagesmentioning

confidence: 99%

Immune Cells and Molecular Mediators in the Pathogenesis of the Abdominal Aortic Aneurysm

Rizas

Ippagunta²,

Tilson³

2009

Cardiology in Review

134

105

View full text Add to dashboard Cite

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“…Primary rat macrophage isolation was performed as previously described (31). Wistar rats (12-to 20-wk-old males) were injected with 20 ml of 2% glycogen (Sigma-Aldrich).…”

Section: Isolation Of Rat Macrophagesmentioning

confidence: 99%

Monocyte Chemoattractant Protein-1 (CCL-2) Integrates Mechanical and Endocrine Signals That Mediate Term and Preterm Labor

Shynlova

Tsui

Dorogin

et al. 2008

The Journal of Immunology

142

126

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Recent evidence suggests that leukocytes infiltrate uterine tissues at or around the time of parturition, implicating inflammation as a key mechanism of human labor. MCP-1 (also known as C-C chemokine motif ligand 2, CCL-2) is a proinflammatory cytokine that is up-regulated in human myometrium during labor. Myometrium was collected from pregnant rats across gestation and at labor. Total RNA and proteins were subjected to real-time PCR and ELISA, respectively. Ccl-2 gene and protein expression was significantly up-regulated in the gravid rat myometrium before and during labor, which might suggest that it is regulated positively by mechanical stretch of the uterus imposed by the growing fetus and negatively by physiological withdrawal of progesterone (P4). We confirmed in vivo that: 1) administration of P4 receptor antagonist RU486 induced an increase in Ccl-2 mRNA and preterm labor, whereas 2) artificial maintenance of elevated P4 levels at late gestation caused a significant decrease in gene expression and blocked labor; 3) Ccl-2 was elevated specifically in the gravid horn of unilaterally pregnant rats suggesting that mechanical strain imposed by the growing fetus controls its expression in the myometrium; 4) in vitro static mechanical stretch of primary rat myometrial smooth muscle cells (25% elongation) induced a release of Ccl-2 protein, which was repressed by pretreatment with P4 (1 μM); and 5) stretch enhanced their monocyte chemoattractant activity. These data indicate that Ccl-2 protein serves to integrate mechanical and endocrine signals contributing to uterine inflammation and the induction of labor and thus may represent a novel target for therapeutic prevention of preterm labor in humans.

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“…9,20 We used a 10 Ϫ8 M concentration of VGVAPG, which was previously shown to be most effective in the induction of macrophage migration and aggregation and dendritic cell fusion. 8,9 The addition of the elastin-derived hexapeptide induced almost a 2-fold increase in the rate of macrophage fusion ( Figure 4A-C), resulting in the generation of some giant cells containing more than 200 nuclei ( Figure 4D). …”

Section: Elastin-derived Hexapeptide (Vgvapg) Increases Macrophage Fumentioning

confidence: 99%

“…Previously, it has been shown that this peptide has a diverse biological activity, including an induction of macrophage migration and aggregation and dendritic cell fusion. 8,9 To show the relevance of MGCs in our mouse model compared with human diseases, we performed immunostaining of human tissues for cathepsin K and observed cathepsin K-positive MGCs in the carotid arteries and abdominal aortic aneurysms. …”

mentioning

confidence: 99%

Cholate-Containing High-Fat Diet Induces the Formation of Multinucleated Giant Cells in Atherosclerotic Plaques of Apolipoprotein E−/− Mice

Samokhin

Wilson

Nho

et al. 2010

ATVB

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Objective-To determine the role of multinucleated giant cells (MGCs) in cardiovascular diseases. Methods and Results-MGCs are a hallmark of giant cell arteritis. They are also described in atherosclerotic plaques from aortic aneurysms and carotid and coronary arteries. Herein, we demonstrate that the cholate-containing Paigen diet yields many MGCs in atherosclerotic plaques of apolipoprotein EϪ/Ϫ mice. These mice revealed a 4-fold increase in MGC numbers when compared with mice on a Western or Paigen diet without cholate. Most of the MGCs stained intensively for cathepsin K and were located at fibrous caps and close to damaged elastic laminae, with associated medial smooth muscle cell depletion. During in vitro experiments, MGCs demonstrated a 6-fold increase in elastolytic activity when compared with macrophages and facilitated transmigration of smooth muscle cells through a collagen-elastin matrix. An elastin-derived hexapeptide (Val-Gly-Val-Ala-Pro-Gly [VGVAPG]) significantly increased the rate of macrophage fusion, providing a possible mechanism of in vivo MGC formation. Comparable to the mouse model, human specimens from carotid arteries and aortic aneurysms contained cathepsin K-positive MGCs. Key Words: multinucleated giant cells Ⅲ cathepsin K Ⅲ atherosclerosis Ⅲ cholate Ⅲ elastin T he presence of multinucleated giant cells (MGCs) in blood vessel walls is well described in patients with giant cell arteritis (GCA). The name of this disease reflects the presence of MGCs formed by the fusion of macrophages in inflammatory infiltrates of the arterial wall. 1,2 In atherosclerosis, MGCs have been described in plaques from aortic aneurysms and carotid and coronary arteries. 3 In 1 report, 4 CD11c-positive MGCs have been observed in advanced atherosclerotic plaques of apolipoprotein E (apoE)Ϫ/Ϫ mice receiving a "Western" high-fat diet (HFD). Conclusion-ApolipoproteinHerein, we report a mouse model that consistently generates MGCs in atherosclerotic lesions. We compared the effect of a cholate-containing Paigen diet with the widely used Western HFD and also with a Paigen diet without cholate and observed that the mice in the first group developed 4 times more cathepsin K (Ctsk)-expressing MGCs than their littermates on cholate-free HFDs. Researchers [5][6][7] have previously shown that cathepsin K is critical for the elastic lamina degradation in atherosclerotic lesions in apoEϪ/Ϫ mice. The identification of MGCs close to elastin fibers and especially in the proximity of elastin fiber breaks prompted us to investigate the effect of cathepsin K deficiency on the ability of MGCs to cleave elastin fibers and to facilitate smooth muscle cell (SMC) migration through an elastin-collagen layer. We also tested the effect of an elastin-derived hexapeptide (Val-Gly-Val-Ala-Pro-Gly [VGVAPG]) on the rate of interleukin (IL) 4 -induced fusion of thioglycolate-elicited peritoneal macrophages. Previously, it has been shown that this peptide has a diverse biological activity, including an induction of macrophage migration and agg...

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Induction of macrophage migration through lactose‐insensitive receptor by elastin‐derived nonapeptides and their analog

Cited by 33 publications

References 28 publications

Immune Cells and Molecular Mediators in the Pathogenesis of the Abdominal Aortic Aneurysm

Immune Cells and Molecular Mediators in the Pathogenesis of the Abdominal Aortic Aneurysm

Monocyte Chemoattractant Protein-1 (CCL-2) Integrates Mechanical and Endocrine Signals That Mediate Term and Preterm Labor

Cholate-Containing High-Fat Diet Induces the Formation of Multinucleated Giant Cells in Atherosclerotic Plaques of Apolipoprotein E−/− Mice

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