IL-1β-Mediated Activation of Adipose-Derived Mesenchymal Stromal Cells Results in PMN Reallocation and Enhanced Phagocytosis: A Possible Mechanism for the Reduction of Osteoarthritis Pathology
Background: Injection of adipose-derived mesenchymal stromal cells (ASCs) into murine knee joints after induction of inflammatory collagenase-induced osteoarthritis (CiOA) reduces development of joint pathology. This protection is only achieved when ASCs are applied in early CiOA, which is character...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01075/full |
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| author | Stephanie C. M. van Dalen Arjen B. Blom Birgitte Walgreen Annet W. Slöetjes Monique M. A. Helsen Edwin J. W. Geven Menno ter Huurne Thomas Vogl Johannes Roth Fons A. J. van de Loo Marije I. Koenders Louis Casteilla Peter M. van der Kraan Martijn H. J. van den Bosch Peter L. E. M. van Lent |
| author_facet | Stephanie C. M. van Dalen Arjen B. Blom Birgitte Walgreen Annet W. Slöetjes Monique M. A. Helsen Edwin J. W. Geven Menno ter Huurne Thomas Vogl Johannes Roth Fons A. J. van de Loo Marije I. Koenders Louis Casteilla Peter M. van der Kraan Martijn H. J. van den Bosch Peter L. E. M. van Lent |
| author_sort | Stephanie C. M. van Dalen |
| collection | DOAJ |
| description | Background: Injection of adipose-derived mesenchymal stromal cells (ASCs) into murine knee joints after induction of inflammatory collagenase-induced osteoarthritis (CiOA) reduces development of joint pathology. This protection is only achieved when ASCs are applied in early CiOA, which is characterized by synovitis and high S100A8/A9 and IL-1β levels, suggesting that inflammation is a prerequisite for the protective effect of ASCs. Our objective was to gain more insight into the interplay between synovitis and ASC-mediated amelioration of CiOA pathology.Methods: CiOA was induced by intra-articular collagenase injection. Knee joint sections were stained with hematoxylin/eosin and immunolocalization of polymorphonuclear cells (PMNs) and ASCs was performed using antibodies for NIMP-R14 and CD271, respectively. Chemokine expression induced by IL-1β or S100A8/A9 was assessed with qPCR and Luminex. ASC-PMN co-cultures were analyzed microscopically and with Luminex for inflammatory mediators. Migration of PMNs through transwell membranes toward conditioned medium of non-stimulated ASCs (ASCNS-CM) or IL-1β-stimulated ASCs (ASCIL-1β-CM) was examined using flow cytometry. Phagocytic capacity of PMNs was measured with labeled zymosan particles.Results: Intra-articular saline injection on day 7 of CiOA increased synovitis after 6 h, characterized by PMNs scattered throughout the joint cavity and the synovium. ASC injection resulted in comparable numbers of PMNs which clustered around ASCs in close interaction with the synovial lining. IL-1β-stimulation of ASCs in vitro strongly increased expression of PMN-attracting chemokines CXCL5, CXCL7, and KC, whereas S100A8/A9-stimulation did not. In agreement, the number of clustered PMNs per ASC was significantly increased after 6 h of co-culturing with IL-1β-stimulated ASCs. Also migration of PMNs toward ASCIL-1β-CM was significantly enhanced (287%) when compared to ASCNS-CM. Interestingly, association of PMNs with ASCs significantly diminished KC protein release by ASCs (69% lower after 24 h), accompanied by reduced release of S100A8/A9 protein by the PMNs. Moreover, phagocytic capacity of PMNs was strongly enhanced after priming with ASCIL-1β-CM.Conclusions: Local application of ASCs in inflamed CiOA knee joints results in clustering of attracted PMNs with ASCs in the synovium, which is likely mediated by IL-1β-induced up-regulation of chemokine release by ASCs. This results in enhanced phagocytic capacity of PMNs, enabling the clearance of debris to attenuate synovitis. |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-16T09:16:39Z |
| publishDate | 2019-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-6ad2b9a22dd747d49bfb41f920fc06d92022-12-21T22:36:52ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-05-011010.3389/fimmu.2019.01075440688IL-1β-Mediated Activation of Adipose-Derived Mesenchymal Stromal Cells Results in PMN Reallocation and Enhanced Phagocytosis: A Possible Mechanism for the Reduction of Osteoarthritis PathologyStephanie C. M. van Dalen0Arjen B. Blom1Birgitte Walgreen2Annet W. Slöetjes3Monique M. A. Helsen4Edwin J. W. Geven5Menno ter Huurne6Thomas Vogl7Johannes Roth8Fons A. J. van de Loo9Marije I. Koenders10Louis Casteilla11Peter M. van der Kraan12Martijn H. J. van den Bosch13Peter L. E. M. van Lent14Experimental Rheumatology, Department of Rheumatology, Radboud University Medical Center, Nijmegen, NetherlandsExperimental Rheumatology, Department of Rheumatology, Radboud University Medical Center, Nijmegen, NetherlandsExperimental Rheumatology, Department of Rheumatology, Radboud University Medical Center, Nijmegen, NetherlandsExperimental Rheumatology, Department of Rheumatology, Radboud University Medical Center, Nijmegen, NetherlandsExperimental Rheumatology, Department of Rheumatology, Radboud University Medical Center, Nijmegen, NetherlandsExperimental Rheumatology, Department of Rheumatology, Radboud University Medical Center, Nijmegen, NetherlandsExperimental Rheumatology, Department of Rheumatology, Radboud University Medical Center, Nijmegen, NetherlandsInstitute of Immunology, University of Münster, Münster, GermanyInstitute of Immunology, University of Münster, Münster, GermanyExperimental Rheumatology, Department of Rheumatology, Radboud University Medical Center, Nijmegen, NetherlandsExperimental Rheumatology, Department of Rheumatology, Radboud University Medical Center, Nijmegen, NetherlandsSTROMALab, University of Toulouse, Toulouse, FranceExperimental Rheumatology, Department of Rheumatology, Radboud University Medical Center, Nijmegen, NetherlandsExperimental Rheumatology, Department of Rheumatology, Radboud University Medical Center, Nijmegen, NetherlandsExperimental Rheumatology, Department of Rheumatology, Radboud University Medical Center, Nijmegen, NetherlandsBackground: Injection of adipose-derived mesenchymal stromal cells (ASCs) into murine knee joints after induction of inflammatory collagenase-induced osteoarthritis (CiOA) reduces development of joint pathology. This protection is only achieved when ASCs are applied in early CiOA, which is characterized by synovitis and high S100A8/A9 and IL-1β levels, suggesting that inflammation is a prerequisite for the protective effect of ASCs. Our objective was to gain more insight into the interplay between synovitis and ASC-mediated amelioration of CiOA pathology.Methods: CiOA was induced by intra-articular collagenase injection. Knee joint sections were stained with hematoxylin/eosin and immunolocalization of polymorphonuclear cells (PMNs) and ASCs was performed using antibodies for NIMP-R14 and CD271, respectively. Chemokine expression induced by IL-1β or S100A8/A9 was assessed with qPCR and Luminex. ASC-PMN co-cultures were analyzed microscopically and with Luminex for inflammatory mediators. Migration of PMNs through transwell membranes toward conditioned medium of non-stimulated ASCs (ASCNS-CM) or IL-1β-stimulated ASCs (ASCIL-1β-CM) was examined using flow cytometry. Phagocytic capacity of PMNs was measured with labeled zymosan particles.Results: Intra-articular saline injection on day 7 of CiOA increased synovitis after 6 h, characterized by PMNs scattered throughout the joint cavity and the synovium. ASC injection resulted in comparable numbers of PMNs which clustered around ASCs in close interaction with the synovial lining. IL-1β-stimulation of ASCs in vitro strongly increased expression of PMN-attracting chemokines CXCL5, CXCL7, and KC, whereas S100A8/A9-stimulation did not. In agreement, the number of clustered PMNs per ASC was significantly increased after 6 h of co-culturing with IL-1β-stimulated ASCs. Also migration of PMNs toward ASCIL-1β-CM was significantly enhanced (287%) when compared to ASCNS-CM. Interestingly, association of PMNs with ASCs significantly diminished KC protein release by ASCs (69% lower after 24 h), accompanied by reduced release of S100A8/A9 protein by the PMNs. Moreover, phagocytic capacity of PMNs was strongly enhanced after priming with ASCIL-1β-CM.Conclusions: Local application of ASCs in inflamed CiOA knee joints results in clustering of attracted PMNs with ASCs in the synovium, which is likely mediated by IL-1β-induced up-regulation of chemokine release by ASCs. This results in enhanced phagocytic capacity of PMNs, enabling the clearance of debris to attenuate synovitis.https://www.frontiersin.org/article/10.3389/fimmu.2019.01075/fullCiOAsynovitisadipose-derived mesenchymal stromal cellsinterleukin-1βchemokinesPMNs |
| spellingShingle | Stephanie C. M. van Dalen Arjen B. Blom Birgitte Walgreen Annet W. Slöetjes Monique M. A. Helsen Edwin J. W. Geven Menno ter Huurne Thomas Vogl Johannes Roth Fons A. J. van de Loo Marije I. Koenders Louis Casteilla Peter M. van der Kraan Martijn H. J. van den Bosch Peter L. E. M. van Lent IL-1β-Mediated Activation of Adipose-Derived Mesenchymal Stromal Cells Results in PMN Reallocation and Enhanced Phagocytosis: A Possible Mechanism for the Reduction of Osteoarthritis Pathology Frontiers in Immunology CiOA synovitis adipose-derived mesenchymal stromal cells interleukin-1β chemokines PMNs |
| title | IL-1β-Mediated Activation of Adipose-Derived Mesenchymal Stromal Cells Results in PMN Reallocation and Enhanced Phagocytosis: A Possible Mechanism for the Reduction of Osteoarthritis Pathology |
| title_full | IL-1β-Mediated Activation of Adipose-Derived Mesenchymal Stromal Cells Results in PMN Reallocation and Enhanced Phagocytosis: A Possible Mechanism for the Reduction of Osteoarthritis Pathology |
| title_fullStr | IL-1β-Mediated Activation of Adipose-Derived Mesenchymal Stromal Cells Results in PMN Reallocation and Enhanced Phagocytosis: A Possible Mechanism for the Reduction of Osteoarthritis Pathology |
| title_full_unstemmed | IL-1β-Mediated Activation of Adipose-Derived Mesenchymal Stromal Cells Results in PMN Reallocation and Enhanced Phagocytosis: A Possible Mechanism for the Reduction of Osteoarthritis Pathology |
| title_short | IL-1β-Mediated Activation of Adipose-Derived Mesenchymal Stromal Cells Results in PMN Reallocation and Enhanced Phagocytosis: A Possible Mechanism for the Reduction of Osteoarthritis Pathology |
| title_sort | il 1β mediated activation of adipose derived mesenchymal stromal cells results in pmn reallocation and enhanced phagocytosis a possible mechanism for the reduction of osteoarthritis pathology |
| topic | CiOA synovitis adipose-derived mesenchymal stromal cells interleukin-1β chemokines PMNs |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.01075/full |
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