Annexin A1: a central player in the anti-inflammatory and neuroprotective role of microglia

McArthur, S., Cristante, E., Paterno, M., Christian, H.C., Roncaroli, F., Gillies, G.E. and Solito, E. 2010. Annexin A1: a central player in the anti-inflammatory and neuroprotective role of microglia. Journal of Immunology. 185 (10), pp. 6317-6328. https://doi.org/10.4049/jimmunol.1001095

TitleAnnexin A1: a central player in the anti-inflammatory and neuroprotective role of microglia
AuthorsMcArthur, S., Cristante, E., Paterno, M., Christian, H.C., Roncaroli, F., Gillies, G.E. and Solito, E.
Abstract

The brain microenvironment is continuously monitored by microglia with the detection of apoptotic cells or pathogens being rapidly followed by their phagocytosis to prevent inflammatory responses. The protein annexin A1 (ANXA1) is key to the phagocytosis of apoptotic leukocytes during peripheral inflammatory resolution, but the pathophysiological significance of its expression in the CNS that is restricted almost exclusively to microglia is unclear. In this study, we test the hypothesis that ANXA1 is important in the microglial clearance of apoptotic neurons in both noninflammatory and inflammatory conditions. We have identified ANXA1 to be sparingly expressed in microglia of normally aged human brains and to be more strongly expressed in Alzheimer's disease. Using an in vitro model comprising microglial and neuronal cell lines, as well as primary microglia from wild-type and ANXA1 null mice, we have identified two distinct roles for microglial ANXA1: 1) controlling the noninflammatory phagocytosis of apoptotic neurons and 2) promoting resolution of inflammatory microglial activation. In particular, we showed that microglial-derived ANXA1 targets apoptotic neurons, serving as both an "eat me" signal and a bridge between phosphatidylserine on the dying cell and formyl peptide receptor 2 on the phagocytosing microglia. Moreover, inflammatory activation of microglia impairs their ability to discriminate between apoptotic and nonapoptotic cells, an ability restored by exogenous ANXA1. We thus show that ANXA1 is fundamental for brain homeostasis, and we suggest that ANXA1 and its peptidomimetics can be novel therapeutic targets in neuroinflammation.

JournalJournal of Immunology
Journal citation185 (10), pp. 6317-6328
ISSN1550-6606
Year2010
PublisherAmerican Association of Immunologists
Digital Object Identifier (DOI)https://doi.org/10.4049/jimmunol.1001095
Web address (URL)http://dx.doi.org/10.4049/jimmunol.1001095
Publication dates
Published2010

Related outputs

Stimulation of the Pro-Resolving Receptor Fpr2 Reverses Inflammatory Microglial Activity by Suppressing NFκB Activity
Edward S. Wickstead, Bradley T. Elliott, Sarah Pokorny, Christopher Biggs, Stephen J. Getting and Simon McArthur 2023. Stimulation of the Pro-Resolving Receptor Fpr2 Reverses Inflammatory Microglial Activity by Suppressing NFκB Activity. International Journal of Molecular Sciences. 24 (21). https://doi.org/10.3390/ijms242115996

The restorative role of annexin A1 at the blood–brain barrier
McArthur, S., Azevedo Loila, R, Maggioli, E, Errede, M, Virgintino, D and Solito, E 2016. The restorative role of annexin A1 at the blood–brain barrier. Fluids & Barriers of the CNS. 13, pp. 17-33. https://doi.org/10.1186/s12987-016-0043-0

Counteractive effects of antenatal glucocorticoid treatment on D1 receptor modulation of spatial working memory
Virdee, K., Kentrop, J., Jupp, B., Venus, B., Hensman, D., McArthur, S., Wilkinson, J., Robbins, T.W., Gillies, G.E. and Dalley, J.W. 2016. Counteractive effects of antenatal glucocorticoid treatment on D1 receptor modulation of spatial working memory. Psychopharmacology. 233 (21), pp. 3751-3761. https://doi.org/10.1007/s00213-016-4405-8

Estrogen protects the blood–brain barrier from inflammation-induced disruption and increased lymphocyte trafficking
Maggioli, E., McArthur, S., Mauro, C., Kieswich, J., Kusters, D.H.M., Reutelingsperger, C.P.M., Yaqoob, M.M. and Solito, E. 2015. Estrogen protects the blood–brain barrier from inflammation-induced disruption and increased lymphocyte trafficking. Brain Behavior & Immunity. 51, p. 212–222. https://doi.org/10.1016/j.bbi.2015.08.020

Definition of a Novel Pathway Centered on Lysophosphatidic Acid To Recruit Monocytes during the Resolution Phase of Tissue Inflammation.
McArthur, S., Gobbetti, T., Kusters, D.H.M., Reutelingsperger, C.P.M., Flower, R.J. and Perretti, M. 2015. Definition of a Novel Pathway Centered on Lysophosphatidic Acid To Recruit Monocytes during the Resolution Phase of Tissue Inflammation. Journal of Immunology. 195 (3), pp. 1139-1151. https://doi.org/10.4049/jimmunol.1500733

Sex-specific disruption of murine midbrain astrocytic and dopaminergic developmental trajectories following antenatal GC treatment
McArthur, S., Pienaar, I.S., Siddiqi, S.M., Gillies, G.E. and Mazhar-Siddiqi, S. 2015. Sex-specific disruption of murine midbrain astrocytic and dopaminergic developmental trajectories following antenatal GC treatment. Brain Stucture & Function. https://doi.org/10.1007/s00429-015-1049-0

Astroglial Plasticity Is Implicated in Hippocampal Remodelling in Adult Rats Exposed to Antenatal Dexamethasone
Shende Vishvesh, McArthur, S. and Opacka-Juffry Jolanta 2015. Astroglial Plasticity Is Implicated in Hippocampal Remodelling in Adult Rats Exposed to Antenatal Dexamethasone. Neural Plasticity. 2015, p. Article ID 694347 694347. https://doi.org/10.1155/2015/694347

Nonredundant protective properties of FPR2/ALX in polymicrobial murine sepsis
Gobbetti, T., Coldewey, S.M., Chen, J., McArthur, S., le Faouder, P., Cenac, N., Flower, R.J., Thiemermann, C. and Perretti, M. 2014. Nonredundant protective properties of FPR2/ALX in polymicrobial murine sepsis. Proceedings of the National Academy of Sciences. 111 (52), pp. 18685-90. https://doi.org/10.1073/pnas.1410938111

Identification of a Novel Recycling Sequence in the C-tail of FPR2/ALX Receptor: Association with Cell Protection from Apoptosis
Thompson, D., McArthur, S., Hislop, J.N., Flower, R.J., Perretti, M. and James N. Hislop 2014. Identification of a Novel Recycling Sequence in the C-tail of FPR2/ALX Receptor: Association with Cell Protection from Apoptosis. Journal of Biological Chemistry. 289 (52), pp. 36166-78. https://doi.org/10.1074/jbc.M114.612630

Antenatal glucocorticoid treatment induces adaptations in adult midbrain dopamine neurons, which underpin sexually dimorphic behavioral resilience
Virdee, K., McArthur, S., Brischoux, F., Caprioli, D., Ungless, M.A., Robbins, T.W., Dalley, J.W. and Gillies, G.E. 2014. Antenatal glucocorticoid treatment induces adaptations in adult midbrain dopamine neurons, which underpin sexually dimorphic behavioral resilience. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 39 (2), pp. 339-350. https://doi.org/10.1038/npp.2013.196

Endogenous annexin A1 is a novel protective determinant in nonalcoholic steatohepatitis in mice
Locatelli, I., Sutti, S., Jindal, A., Vacchiano, M., Bozzola, C., Reutelingsperger, C.P.M., Kusters, D.H.M., Bena, S., Parola, M., Paternostro, C., Bugianesi, E., McArthur, S., Albano, E. and Perretti, M. 2014. Endogenous annexin A1 is a novel protective determinant in nonalcoholic steatohepatitis in mice. Hepatology. 60 (2), pp. 531-544. https://doi.org/10.1002/hep.27141

Sex-dependent diversity in ventral tegmental dopaminergic neurons and developmental programing: a molecular, cellular and behavioral analysis
Gillies, G.E., Virdee, K., McArthur, S. and Dalley, J.W. 2014. Sex-dependent diversity in ventral tegmental dopaminergic neurons and developmental programing: a molecular, cellular and behavioral analysis. Neuroscience. 282C, pp. 69-85. https://doi.org/10.1016/j.neuroscience.2014.05.033

Ligand-specific conformational change of the G-protein-coupled receptor ALX/FPR2 determines proresolving functional responses
Cooray, S.N., Gobbetti, T., Montero-Melendez, T., McArthur, S., Thompson, D., Clark, A.J.L., Flower, R.J. and Perretti, M. 2013. Ligand-specific conformational change of the G-protein-coupled receptor ALX/FPR2 determines proresolving functional responses. Proceedings of the National Academy of Sciences of the United States of America. 110 (45), pp. 18232-18237. https://doi.org/10.1073/pnas.1308253110

Prazosin, an α(1)-adrenoceptor antagonist, prevents memory deterioration in the APP23 transgenic mouse model of Alzheimer's disease
Katsouri, L., Vizcaychipi, M.P., McArthur, S., Harrison, I., Suárez-Calvet, M., Lleo, A., Lloyd, D.G., Ma, D. and Sastre, M. 2013. Prazosin, an α(1)-adrenoceptor antagonist, prevents memory deterioration in the APP23 transgenic mouse model of Alzheimer's disease. Neurobiology of Aging. 34 (4), pp. 1105-15. https://doi.org/10.1016/j.neurobiolaging.2012.09.010

Oestrogen and immunomodulation: new mechanisms that impact on peripheral and central immunity
Nadkarni, S. and McArthur, S. 2013. Oestrogen and immunomodulation: new mechanisms that impact on peripheral and central immunity. Current Opinion in Pharmacology. 13 (4), pp. 576-581. https://doi.org/10.1016/j.coph.2013.05.007

Identification of an essential endogenous regulator of blood-brain barrier integrity, and its pathological and therapeutic implications
Cristante, E., McArthur, S., Mauro, C., Maggioli, E., Romero, I.A., Wylezinska-Arridge, M., Couraud, P.O., Lopez-Tremoleda, J., Christian, H.C., Weksler, B.B., Malaspina, A. and Solito, E. 2013. Identification of an essential endogenous regulator of blood-brain barrier integrity, and its pathological and therapeutic implications. Proceedings of the National Academy of Sciences of the United States of America. 110 (3), pp. 832-841. https://doi.org/10.1073/pnas.1209362110

Chemerin15 inhibits neutrophil-mediated vascular inflammation and myocardial ischemia-reperfusion injury through ChemR23
Cash, J.L., Bena, S., Headland, S.E., McArthur, S., Brancaleone, V. and Perretti, M. 2013. Chemerin15 inhibits neutrophil-mediated vascular inflammation and myocardial ischemia-reperfusion injury through ChemR23. EMBO reports. 14 (11), pp. 999-1007. https://doi.org/10.1038/embor.2013.138

Annexin A1 N-terminal derived Peptide ac2-26 exerts chemokinetic effects on human neutrophils
Dalli, J., Montero-Melendez, T., McArthur, S. and Perretti, M. 2012. Annexin A1 N-terminal derived Peptide ac2-26 exerts chemokinetic effects on human neutrophils. Frontiers in Pharmacology. 3 28. https://doi.org/10.3389/fphar.2012.00028

Novel ontogenetic patterns of sexual differentiation in arcuate nucleus GHRH neurons revealed in GHRH-enhanced green fluorescent protein transgenic mice
McArthur, S., Robinson, I.C. and Gillies, G.E. 2011. Novel ontogenetic patterns of sexual differentiation in arcuate nucleus GHRH neurons revealed in GHRH-enhanced green fluorescent protein transgenic mice. Endocrinology. 152 (2), pp. 607-617. https://doi.org/10.1210/en.2010-0798

Peripheral vs. central sex steroid hormones in experimental Parkinson's disease
McArthur, S. and Gillies, G.E. 2011. Peripheral vs. central sex steroid hormones in experimental Parkinson's disease. Frontiers in Endocrinology. 2 82. https://doi.org/10.3389/fendo.2011.00082

Antiallergic cromones inhibit neutrophil recruitment onto vascular endothelium via Annexin-A1 mobilization
Yazid, S., Leoni, G., Getting, S.J., Cooper, D., Solito, E., Perretti, M. and Flower, R.J. 2010. Antiallergic cromones inhibit neutrophil recruitment onto vascular endothelium via Annexin-A1 mobilization. Arteriosclerosis, Thrombosis, and Vascular Biology. 30 (9), pp. 1718-1724. https://doi.org/10.1161/ATVBAHA.110.209536

Estrogen actions in the brain and the basis for differential action in men and women: a case for sex-specific medicines
Gillies, G.E. and McArthur, S. 2010. Estrogen actions in the brain and the basis for differential action in men and women: a case for sex-specific medicines. Pharmacological reviews. 62 (2), pp. 155-198. https://doi.org/10.1124/pr.109.002071

Anti-allergic drugs and the Annexin-A1 system
Yazid, S., Ayoub, S.S., Solito, E., McArthur, S., Vo, P., Dufton, N. and Flower, R.J. 2010. Anti-allergic drugs and the Annexin-A1 system. Pharmacological reports. 62 (3), pp. 511-517. https://doi.org/10.1016/S1734-1140(10)70307-8

Independent influences of sex steroids of systemic and central origin in a rat model of Parkinson's disease: a contribution to sex-specific neuroprotection by estrogens
Gillies, G.E. and McArthur, S. 2010. Independent influences of sex steroids of systemic and central origin in a rat model of Parkinson's disease: a contribution to sex-specific neuroprotection by estrogens. Hormones and behavior. 57 (1), pp. 23-34. https://doi.org/10.1016/j.yhbeh.2009.06.002

Cromoglycate drugs suppress eicosanoid generation in U937 cells by promoting the release of Anx-A1
Yazid, S., Solito, E., Christian, H.C., McArthur, S., Goulding, N. and Flower, R.J. 2009. Cromoglycate drugs suppress eicosanoid generation in U937 cells by promoting the release of Anx-A1. Biochemical Pharmacology. 77 (12), pp. 1814-1826. https://doi.org/10.1016/j.bcp.2009.03.010

Annexin A1 regulates hormone exocytosis through a mechanism involving actin reorganization
McArthur, S., Yazid, S., Christian, H.C., Sirha, R., Flower, R.J., Buckingham, J.C. and Solito, E. 2009. Annexin A1 regulates hormone exocytosis through a mechanism involving actin reorganization. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 23 (11), pp. 4000-4010. https://doi.org/10.1096/fj.09-131391

Annexin A1 in the brain: undiscovered roles?
Solito, E., McArthur, S., Christian, H.C., Gavins, F.N.E., Buckingham, J.C. and Gillies, G.E. 2008. Annexin A1 in the brain: undiscovered roles? Trends in Pharmacological Sciences. 29 (3), pp. 135-42. https://doi.org/10.1016/j.tips.2007.12.003

Striatal susceptibility to a dopaminergic neurotoxin is independent of sex hormone effects on cell survival and DAT expression but is exacerbated by central aromatase inhibition
McArthur, S., Murray, H.E., Dhankot, A., Dexter, D.T. and Gillies, G.E. 2007. Striatal susceptibility to a dopaminergic neurotoxin is independent of sex hormone effects on cell survival and DAT expression but is exacerbated by central aromatase inhibition. Journal of Neurochemistry. 100 (3), pp. 678-692. https://doi.org/10.1111/j.1471-4159.2006.04226.x

The size and distribution of midbrain dopaminergic populations are permanently altered by perinatal glucocorticoid exposure in a sex- region- and time-specific manner
McArthur, S., McHale, E. and Gillies, G.E. 2007. The size and distribution of midbrain dopaminergic populations are permanently altered by perinatal glucocorticoid exposure in a sex- region- and time-specific manner. Neuropsychopharmacology. 32 (7), pp. 1462-1476. https://doi.org/10.1038/sj.npp.1301277

Perinatal glucocorticoid treatment disrupts the hypothalamo-lactotroph axis in adult female, but not male, rats
McArthur, S., Siddique, Z.L., Christian, H.C., Capone, G., Theogaraj, E., John, C.D., Smith, S.F., Morris, J.F., Buckingham, J.C. and Gillies, G.E. 2006. Perinatal glucocorticoid treatment disrupts the hypothalamo-lactotroph axis in adult female, but not male, rats. Endocrinology. 147 (4), pp. 1904-1915. https://doi.org/10.1210/en.2005-1496

Altered mesencephalic dopaminergic populations in adulthood as a consequence of brief perinatal glucocorticoid exposure
McArthur, S., McHale, E., Dalley, J.W., Buckingham, J.C. and Gillies, G.E. 2005. Altered mesencephalic dopaminergic populations in adulthood as a consequence of brief perinatal glucocorticoid exposure. Journal of Neuroendocrinology. 17 (8), pp. 475-482. https://doi.org/10.1111/j.1365-2826.2005.01331.x

MC-3 receptor and the inflammatory mechanisms activated in acute myocardial infarct
Getting, S.J., Di Filippo, C., Christian, H.C., Lam, C.W., Rossi, F., D'Amico, M. and Perretti, M. 2004. MC-3 receptor and the inflammatory mechanisms activated in acute myocardial infarct. Journal of Leukocyte Biology. 76 (4), pp. 845-853. https://doi.org/10.1189/jlb.0306175

Sex dimorphisms in the neuroprotective effects of estrogen in an animal model of Parkinson's disease
Gillies, G.E., Murray, H.E., Dexter, D.T. and McArthur, S. 2004. Sex dimorphisms in the neuroprotective effects of estrogen in an animal model of Parkinson's disease. Pharmacology, biochemistry, and behavior. 78 (3), pp. 513-522. https://doi.org/10.1016/j.pbb.2004.04.022

The annexin 1-/- mouse: phenotypic studies
Wells, D., Wells, K., Liu, K., Hannon, R., Croxtall, J.D., Damazo, A.S., Oliani, S.M., Getting, S.J., Parente, L., Paul-Clark, M., Yona, S., Gavins, F.N.E., Martin, J., Christian, H.C., Cover, P.O., John, C.D., Solito, E., Morris, J.F., Perretti, M., Buckingham, J.C. and Flower, R.J. 2004. The annexin 1-/- mouse: phenotypic studies. Annexins. 1 (2), pp. 109-120.

Redundancy of a Functional Melanocortin 1 Receptor in the Anti-inflammatory actions of melanocortin peptides: studies in the recessive yellow (e/e) mouse suggest an important role for melanocortin 3 receptor
Getting, S.J., Christian, H.C., Lam, C.W., Gavins, F.N.E., Flower, R.J., Schiöth, H.B. and Perretti, M. 2003. Redundancy of a Functional Melanocortin 1 Receptor in the Anti-inflammatory actions of melanocortin peptides: studies in the recessive yellow (e/e) mouse suggest an important role for melanocortin 3 receptor. Journal of Immunology. 170 (6), pp. 3323-3330.

Dose- and sex-dependent effects of the neurotoxin 6-hydroxydopamine on the nigrostriatal dopaminergic pathway of adult rats: differential actions of estrogen in males and females
Murray, H.E., Pillai, A.V., McArthur, S., Razvi, N., Datla, K.P., Dexter, D.T. and Gillies, G.E. 2003. Dose- and sex-dependent effects of the neurotoxin 6-hydroxydopamine on the nigrostriatal dopaminergic pathway of adult rats: differential actions of estrogen in males and females. Neuroscience. 116 (1), pp. 213-222. https://doi.org/10.1016/S0306-4522(02)00578-X

Endogenous lipid- and peptide-derived anti-inflammatory pathways generated with glucocorticoid and aspirin treatment activate the lipoxin A4 receptor
Perretti, M., Chiang, N., La, M., Fierro, I.M., Marullo, S., Getting, S.J., Solito, E. and Serhan, C.N. 2002. Endogenous lipid- and peptide-derived anti-inflammatory pathways generated with glucocorticoid and aspirin treatment activate the lipoxin A4 receptor. Nature Medicine. 8 (11), pp. 1296-1302. https://doi.org/10.1038/nm786

Activation of melanocortin type 3 receptor as a molecular mechanism for adrenocorticotropic hormone efficacy in gouty arthritis
Getting, S.J., Christian, H.C., Flower, R.J. and Perretti, M. 2002. Activation of melanocortin type 3 receptor as a molecular mechanism for adrenocorticotropic hormone efficacy in gouty arthritis. Arthritis & Rheumatism. 46 (10), pp. 2765-2775. https://doi.org/10.1002/art.10526

Involvement of the receptor for formylated peptides in the in vivo anti-migratory actions of annexin 1 and its mimetics
Perretti, M., Getting, S.J., Solito, E., Murphy, P.M. and Gao, J.L. 2001. Involvement of the receptor for formylated peptides in the in vivo anti-migratory actions of annexin 1 and its mimetics. American Journal of Pathology. 158 (6), pp. 1969-1973.

Permalink - https://westminsterresearch.westminster.ac.uk/item/90701/annexin-a1-a-central-player-in-the-anti-inflammatory-and-neuroprotective-role-of-microglia


Share this

Usage statistics

189 total views
0 total downloads
These values cover views and downloads from WestminsterResearch and are for the period from September 2nd 2018, when this repository was created.