Impact of endoplasmic reticulum aminopeptidases 1 (ERAP1) and 2 (ERAP2) on neutrophil cellular functions
IntroductionEndoplasmic reticulum aminopeptidases 1 (ERAP1) and 2 (ERAP2) modulate a plethora of physiological processes for the maintenance of homeostasis in different cellular subsets at both intra and extracellular level.Materials and methodsIn this frame, the extracellular supplementation of rec...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2024.1506216/full |
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| author | Irma Saulle Irma Saulle Fiona Limanaqi Micaela Garziano Micaela Garziano Maria Luisa Murno Valentina Artusa Valentina Artusa Sergio Strizzi Matteo Giovarelli Carsten Schulte Jacopo Aiello Mario Clerici Mario Clerici Claudia Vanetti Mara Biasin |
| author_facet | Irma Saulle Irma Saulle Fiona Limanaqi Micaela Garziano Micaela Garziano Maria Luisa Murno Valentina Artusa Valentina Artusa Sergio Strizzi Matteo Giovarelli Carsten Schulte Jacopo Aiello Mario Clerici Mario Clerici Claudia Vanetti Mara Biasin |
| author_sort | Irma Saulle |
| collection | DOAJ |
| description | IntroductionEndoplasmic reticulum aminopeptidases 1 (ERAP1) and 2 (ERAP2) modulate a plethora of physiological processes for the maintenance of homeostasis in different cellular subsets at both intra and extracellular level.Materials and methodsIn this frame, the extracellular supplementation of recombinant human (rh) ERAP1 and ERAP2 (300 ng/ml) was used to mimic the effect of stressor-induced secretion of ERAPs on neutrophils isolated from 5 healthy subjects. In these cells following 3 h or 24 h rhERAP stimulation by Western Blot, RT-qPCR, Elisa, Confocal microscopy, transwell migration assay, Oxygraphy and Flow Cytometry we assessed: i) rhERAP internalization; ii) activation; iii) migration; iv) oxygen consumption rate; v) reactive oxygen species (ROS) accumulation; granule release; vi) phagocytosis; and vii) autophagy.ResultsWe observed that following stimulation rhERAPs: i) were internalized by neutrophils; ii) triggered their activation as witnessed by increased percentage of MAC-1+CD66b+ expressing neutrophils, cytokine expression/release (IL-1β, IL-8, CCL2, TNFα, IFNγ, MIP-1β) and granule enzyme secretion (myeloperoxidase, Elastase); iii) increased neutrophil migration capacity; iv) increased autophagy and phagocytosis activity; v) reduced ROS accumulation and did not influence oxygen consumption rate.ConclusionOur study provides novel insights into the biological role of ERAPs, and indicates that extracellular ERAPs, contribute to shaping neutrophil homeostasis by promoting survival and tolerance in response to stress-related inflammation. This information could contribute to a better understanding of the biological bases governing immune responses, and to designing ERAP-based therapeutic protocols to control neutrophil-associated human diseases. |
| format | Article |
| id | doaj-art-f5c77ac3131842f89839b2cf9cb50370 |
| institution | Kabale University |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-f5c77ac3131842f89839b2cf9cb503702025-01-07T06:43:49ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-01-011210.3389/fcell.2024.15062161506216Impact of endoplasmic reticulum aminopeptidases 1 (ERAP1) and 2 (ERAP2) on neutrophil cellular functionsIrma Saulle0Irma Saulle1Fiona Limanaqi2Micaela Garziano3Micaela Garziano4Maria Luisa Murno5Valentina Artusa6Valentina Artusa7Sergio Strizzi8Matteo Giovarelli9Carsten Schulte10Jacopo Aiello11Mario Clerici12Mario Clerici13Claudia Vanetti14Mara Biasin15Dipartimento di Scienze Biomediche e Cliniche, Università degli Studi di Milano, Milano, ItalyDipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milano, ItalyDipartimento di Scienze Biomediche e Cliniche, Università degli Studi di Milano, Milano, ItalyDipartimento di Scienze Biomediche e Cliniche, Università degli Studi di Milano, Milano, ItalyDipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milano, ItalyDipartimento di Scienze Biomediche e Cliniche, Università degli Studi di Milano, Milano, ItalyDipartimento di Scienze Biomediche e Cliniche, Università degli Studi di Milano, Milano, ItalyDipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milano, ItalyDipartimento di Scienze Biomediche e Cliniche, Università degli Studi di Milano, Milano, ItalyDipartimento di Scienze Biomediche e Cliniche, Università degli Studi di Milano, Milano, ItalyDipartimento di Scienze Biomediche e Cliniche, Università degli Studi di Milano, Milano, ItalyDipartimento di Scienze Biomediche e Cliniche, Università degli Studi di Milano, Milano, ItalyDipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milano, ItalyIstituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Fondazione Don Carlo Gnocchi, Milano, ItalyDipartimento di Scienze Biomediche e Cliniche, Università degli Studi di Milano, Milano, ItalyDipartimento di Scienze Biomediche e Cliniche, Università degli Studi di Milano, Milano, ItalyIntroductionEndoplasmic reticulum aminopeptidases 1 (ERAP1) and 2 (ERAP2) modulate a plethora of physiological processes for the maintenance of homeostasis in different cellular subsets at both intra and extracellular level.Materials and methodsIn this frame, the extracellular supplementation of recombinant human (rh) ERAP1 and ERAP2 (300 ng/ml) was used to mimic the effect of stressor-induced secretion of ERAPs on neutrophils isolated from 5 healthy subjects. In these cells following 3 h or 24 h rhERAP stimulation by Western Blot, RT-qPCR, Elisa, Confocal microscopy, transwell migration assay, Oxygraphy and Flow Cytometry we assessed: i) rhERAP internalization; ii) activation; iii) migration; iv) oxygen consumption rate; v) reactive oxygen species (ROS) accumulation; granule release; vi) phagocytosis; and vii) autophagy.ResultsWe observed that following stimulation rhERAPs: i) were internalized by neutrophils; ii) triggered their activation as witnessed by increased percentage of MAC-1+CD66b+ expressing neutrophils, cytokine expression/release (IL-1β, IL-8, CCL2, TNFα, IFNγ, MIP-1β) and granule enzyme secretion (myeloperoxidase, Elastase); iii) increased neutrophil migration capacity; iv) increased autophagy and phagocytosis activity; v) reduced ROS accumulation and did not influence oxygen consumption rate.ConclusionOur study provides novel insights into the biological role of ERAPs, and indicates that extracellular ERAPs, contribute to shaping neutrophil homeostasis by promoting survival and tolerance in response to stress-related inflammation. This information could contribute to a better understanding of the biological bases governing immune responses, and to designing ERAP-based therapeutic protocols to control neutrophil-associated human diseases.https://www.frontiersin.org/articles/10.3389/fcell.2024.1506216/fullERAP1ERAP2neutrophilscell migrationphagocytosisautophagy |
| spellingShingle | Irma Saulle Irma Saulle Fiona Limanaqi Micaela Garziano Micaela Garziano Maria Luisa Murno Valentina Artusa Valentina Artusa Sergio Strizzi Matteo Giovarelli Carsten Schulte Jacopo Aiello Mario Clerici Mario Clerici Claudia Vanetti Mara Biasin Impact of endoplasmic reticulum aminopeptidases 1 (ERAP1) and 2 (ERAP2) on neutrophil cellular functions Frontiers in Cell and Developmental Biology ERAP1 ERAP2 neutrophils cell migration phagocytosis autophagy |
| title | Impact of endoplasmic reticulum aminopeptidases 1 (ERAP1) and 2 (ERAP2) on neutrophil cellular functions |
| title_full | Impact of endoplasmic reticulum aminopeptidases 1 (ERAP1) and 2 (ERAP2) on neutrophil cellular functions |
| title_fullStr | Impact of endoplasmic reticulum aminopeptidases 1 (ERAP1) and 2 (ERAP2) on neutrophil cellular functions |
| title_full_unstemmed | Impact of endoplasmic reticulum aminopeptidases 1 (ERAP1) and 2 (ERAP2) on neutrophil cellular functions |
| title_short | Impact of endoplasmic reticulum aminopeptidases 1 (ERAP1) and 2 (ERAP2) on neutrophil cellular functions |
| title_sort | impact of endoplasmic reticulum aminopeptidases 1 erap1 and 2 erap2 on neutrophil cellular functions |
| topic | ERAP1 ERAP2 neutrophils cell migration phagocytosis autophagy |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2024.1506216/full |
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