Extracellular annexin A5: Functions of phosphatidylserine-binding and two-dimensional crystallization

Genderen, Hugo O. van; Kenis, Heidi; Hofstra, Leo; Narula, Jagat; Reutelingsperger, Chris

doi:10.1016/j.bbamcr.2008.01.030

Cited by 192 publications

(164 citation statements)

References 119 publications

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“…Finally, lipid-binding proteins such as annexin A5 (7,37) that recognize exposed phosphatidylserine on apoptotic cells can also be exploited to image dying cells, including apoptotic macrophage foam cells in atherosclerotic lesions. However, because phosphatidylserine can be exposed on any dying or damaged cell, including activated platelets; ischemic, stressed, or traumatized cardiomyocytes; myoblasts; immune cells; and erythrocytes (38,39), opportunities for misinterpretation of data once again arise. Although 99m Tc-EC20 will admittedly image virtually any site of active inflammation, its ease of synthesis and radiolabeling, excellent tissue penetration, and rapid clearance from FR-negative tissues (due to its small size and water solubility (16,25), lack of toxicity or immunogenicity (12,24), and specificity for an abundant cell type in atherosclerotic lesions [macrophages] (12,14,23)) renders it a possible candidate for further evaluation.…”

Section: Discussionmentioning

confidence: 99%

Imaging of Atherosclerosis in Apoliprotein E Knockout Mice: Targeting of a Folate-Conjugated Radiopharmaceutical to Activated Macrophages

Ayala-López¹,

Xia²,

Varghese³

et al. 2010

J Nucl Med

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Early detection of heart disease is essential for the implementation of intervention strategies that reduce the risk of cardiovascular events. Radioimaging methods that have been explored for this purpose include 18 F-FDG, which measures sites of elevated metabolic activity; 99m Tc-annexin A5, which reveals regions of enhanced apoptosis and thrombosis; and 99m Tc-labeled antilectinlike oxidized low-density lipoprotein receptor 1 antibody, which detects the lectinlike oxidized low-density lipoprotein receptor 1 that is overexpressed on a variety of vasculatureassociated cells. In this study, we examine the use of a folatetargeted chelate of 99m Tc, termed 99m Tc-EC20, for imaging of folate receptor (FR)-expressing macrophages that accumulate in atherosclerotic plaques, internalize cholesterol-rich lipoprotein particles, and evolve into foam cells that form components of vulnerable atherosclerotic lesions. Methods: 99m Tc-EC20 was injected into apoliprotein E knockout (apoE2/2) mice fed a normal or Western (high-fat) diet for 25 wk and imaged by g-scintigraphy. Treated mice were also dissected, and radioactivities in excised aortas were quantified by g-counting and imaged by autoradiography. The role of FR-expressing macrophages in uptake of 99m Tc-EC20 was also examined by comparing images of apoE2/2 mice before and after treatment with clodronate liposomes to deplete tissue macrophages, comparing the sites of 99m Tc-EC20 enrichment with sites of macrophage accumulation in thin sections of atherosclerotic tissues, and examining the expression of FRs on atherosclerotic plaquederived macrophages by flow cytometry. Results: ApoE2/2 mice on Western chow exhibited significantly greater accumulation of 99m Tc-EC20 in atherosclerotic lesions than their counterparts on normal chow. The aortas of apoE2/2 mice on a Western diet demonstrated greater numbers of FR-positive macrophages by flow cytometry than did those of apoE2/2 mice on a normal diet. Clodronate liposome treatment significantly reduced the accumulation of 99m Tc-EC20 in atherosclerotic tissues, suggesting that macrophages or monocytes are responsible for uptake of the folate-linked radioimaging agent. Histologic and autoradiographic analysis of tissue sections demonstrated that macrophage accumulation correlated with regions of 99m Tc-EC20 uptake. Conclusion: 99m Tc-EC20 can be used for the imaging of atherosclerosis by selectively targeting FR-positive activated macrophages.

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Section: Discussionmentioning

confidence: 99%

Imaging of Atherosclerosis in Apoliprotein E Knockout Mice: Targeting of a Folate-Conjugated Radiopharmaceutical to Activated Macrophages

Ayala-López¹,

Xia²,

Varghese³

et al. 2010

J Nucl Med

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“…17 Interestingly, some annexins without any secretory signals have been found in the extracellular space (e.g., annexin A1, A2, and A5 of human and annexin B1 of T. solium). 15,[18][19][20] The mechanism by which this occurs remains unclear and is worthy of investigation. 15,21 Recently, proteomic research on E. granulosus has shown that annexin B33 protein (Eg-ANX) could be detected in the excreted/secreted (ES) product and hydatid cyst fluid, which might potentially play important roles in parasite survival mechanisms during infection.…”

Section: Introductionmentioning

confidence: 99%

Characterization of a Secretory Annexin in Echinococcus granulosus

Song¹,

Hu²,

Zhong³

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Abstract. Cystic echinococcosis, caused by Echinococcus granulosus, is a widespread parasitic zoonosis causing economic loss and public health problems. Annexins are important proteins usually present in the plasma membrane, but previous studies have shown that an annexin B33 protein of E. granulosus (Eg-ANX) could be detected in the excretory/ secretory products and cyst fluid. In this study, we cloned and characterized Eg-ANX. In silico analysis showed that the amino acid sequence of Eg-ANX was conserved and lacked any signal peptides. The phospholipid-binding activity of recombinant Eg-ANX (rEg-ANX) was tested; liposomes could bind to rEg-ANX only in the presence of Ca 2+

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“…Annexin A5 is used in a commercial kit to detect early apoptotic cells by its high affinity to phosphatidylserine. This feature may be related to its anti-coagulating activity [22].…”

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confidence: 99%

Immunohistochemical Localization of Annexin A5 in the Mammary Gland of Rats: Up-Regulation of Expression by Pup Removal

Rieanrakwong

Yonezawa

Kurusu

et al. 2010

The Journal of Veterinary Medical Science

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ABSTRACT. The distribution of annexin A5, a cytosolic protein related to gonadotropin releasing hormone action, was examined in the mammary gland of rats by immunohistochemistry with special reference to changes by lactation. Annexin A5 was observed in the interstitial tissues but not alveolar cells in virgin rats, while mammary epithelial cells became positive for annexin A5 in pregnant rats. The intensity of annexin A5 was decreased in lactating rats and dramatically increased after weaning, especially on the nucleus. When pups were removed from their dam at mid-lactation (day 10), annexin A5 was also increased on day 12. Apoptotic epithelial cells detected by terminal deoxynucleotidyl transferase nick end labeling were simultaneously increased. Annexin A5 mRNA expression of mammary tissues was increased after pup removal. These results are the first to demonstrate the distribution of annexin A5 in the mammary glands of lactating rats, and the enhanced expression in mammary epithelial cells after lactation suggests its involvement in mammary epithelial cell involution.KEY WORDS: annexin A5, mammary gland, mammary involution.

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Extracellular annexin A5: Functions of phosphatidylserine-binding and two-dimensional crystallization

Cited by 192 publications

References 119 publications

Imaging of Atherosclerosis in Apoliprotein E Knockout Mice: Targeting of a Folate-Conjugated Radiopharmaceutical to Activated Macrophages

Imaging of Atherosclerosis in Apoliprotein E Knockout Mice: Targeting of a Folate-Conjugated Radiopharmaceutical to Activated Macrophages

Characterization of a Secretory Annexin in Echinococcus granulosus

Immunohistochemical Localization of Annexin A5 in the Mammary Gland of Rats: Up-Regulation of Expression by Pup Removal

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