RNase A Treatment Interferes With Leukocyte Recruitment, Neutrophil Extracellular Trap Formation, and Angiogenesis in Ischemic Muscle Tissue
Background: RNase A (the bovine equivalent to human RNase 1) and RNase 5 (angiogenin) are two closely related ribonucleases. RNase 5 is described as a powerful angiogenic factor. Whether RNase A shares the same angiogenic characteristic, or interferes with vessel growth as demonstrated for arterioge...
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| Format: | Article |
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2020.576736/full |
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| author | Manuel Lasch Manuel Lasch Manuel Lasch Konda Kumaraswami Konda Kumaraswami Simona Nasiscionyte Susanna Kircher Susanna Kircher Dominic van den Heuvel Sarah Meister Hellen Ishikawa-Ankerhold Hellen Ishikawa-Ankerhold Elisabeth Deindl Elisabeth Deindl |
| author_facet | Manuel Lasch Manuel Lasch Manuel Lasch Konda Kumaraswami Konda Kumaraswami Simona Nasiscionyte Susanna Kircher Susanna Kircher Dominic van den Heuvel Sarah Meister Hellen Ishikawa-Ankerhold Hellen Ishikawa-Ankerhold Elisabeth Deindl Elisabeth Deindl |
| author_sort | Manuel Lasch |
| collection | DOAJ |
| description | Background: RNase A (the bovine equivalent to human RNase 1) and RNase 5 (angiogenin) are two closely related ribonucleases. RNase 5 is described as a powerful angiogenic factor. Whether RNase A shares the same angiogenic characteristic, or interferes with vessel growth as demonstrated for arteriogenesis, has never been investigated and is the topic of this present study.Methods and Results: To investigate whether RNase A shows a pro‐ or anti-angiogenic effect, we employed a murine hindlimb model, in which femoral artery ligation (FAL) results in arteriogenesis in the upper leg, and, due to provoked ischemia, in angiogenesis in the lower leg. C57BL/6J male mice underwent unilateral FAL, whereas the contralateral leg was sham operated. Two and seven days after the surgery and intravenous injection of RNase A (50 μg/kg dissolved in saline) or saline (control), the gastrocnemius muscles of mice were isolated from the lower legs for (immuno-) histological analyses. Hematoxylin and Eosin staining evidenced that RNase A treatment resulted in a higher degree of ischemic tissue damage. This was, however, associated with reduced angiogenesis, as evidenced by a reduced capillary/muscle fiber ratio. Moreover, RNase A treatment was associated with a significant reduction in leukocyte infiltration as shown by CD45+ (pan-leukocyte marker), Ly6G+ or MPO+ (neutrophils), MPO+/CitH3+ [neutrophil extracellular traps (NETs)], and CD68+ (macrophages) staining. CD68/MRC1 double staining revealed that RNase A treated mice showed a reduced percentage of M1-like polarized (CD68+/MRC1−) macrophages whereas the percentage of M2-like polarized (CD68+/MRC1+) macrophages was increased.Conclusion: In contrast to RNase 5, RNase A interferes with angiogenesis, which is linked to reduced leukocyte infiltration and NET formation. |
| first_indexed | 2024-12-11T05:43:04Z |
| format | Article |
| id | doaj.art-13104fb8d5c04263b61a8224f369acfe |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-11T05:43:04Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-13104fb8d5c04263b61a8224f369acfe2022-12-22T01:19:04ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2020-11-011110.3389/fphys.2020.576736576736RNase A Treatment Interferes With Leukocyte Recruitment, Neutrophil Extracellular Trap Formation, and Angiogenesis in Ischemic Muscle TissueManuel Lasch0Manuel Lasch1Manuel Lasch2Konda Kumaraswami3Konda Kumaraswami4Simona Nasiscionyte5Susanna Kircher6Susanna Kircher7Dominic van den Heuvel8Sarah Meister9Hellen Ishikawa-Ankerhold10Hellen Ishikawa-Ankerhold11Elisabeth Deindl12Elisabeth Deindl13Walter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, Munich, GermanyBiomedical Center, Institute of Cardiovascular Physiology and Pathophysiology, Ludwig-Maximilians-Universität München, Munich, GermanyDepartment of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Ludwig-Maximilians-Universität München, Munich, GermanyWalter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, Munich, GermanyBiomedical Center, Institute of Cardiovascular Physiology and Pathophysiology, Ludwig-Maximilians-Universität München, Munich, GermanyWalter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, Munich, GermanyWalter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, Munich, GermanyBiomedical Center, Institute of Cardiovascular Physiology and Pathophysiology, Ludwig-Maximilians-Universität München, Munich, GermanyWalter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, Munich, GermanyDepartment of Obstetrics and Gynaecology, University Hospital, Ludwig-Maximilians-Universität München, Munich, GermanyWalter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, Munich, GermanyDepartment of Internal Medicine I, Faculty of Medicine, University Hospital, Ludwig-Maximilians-Universität München, Munich, GermanyWalter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, Munich, GermanyBiomedical Center, Institute of Cardiovascular Physiology and Pathophysiology, Ludwig-Maximilians-Universität München, Munich, GermanyBackground: RNase A (the bovine equivalent to human RNase 1) and RNase 5 (angiogenin) are two closely related ribonucleases. RNase 5 is described as a powerful angiogenic factor. Whether RNase A shares the same angiogenic characteristic, or interferes with vessel growth as demonstrated for arteriogenesis, has never been investigated and is the topic of this present study.Methods and Results: To investigate whether RNase A shows a pro‐ or anti-angiogenic effect, we employed a murine hindlimb model, in which femoral artery ligation (FAL) results in arteriogenesis in the upper leg, and, due to provoked ischemia, in angiogenesis in the lower leg. C57BL/6J male mice underwent unilateral FAL, whereas the contralateral leg was sham operated. Two and seven days after the surgery and intravenous injection of RNase A (50 μg/kg dissolved in saline) or saline (control), the gastrocnemius muscles of mice were isolated from the lower legs for (immuno-) histological analyses. Hematoxylin and Eosin staining evidenced that RNase A treatment resulted in a higher degree of ischemic tissue damage. This was, however, associated with reduced angiogenesis, as evidenced by a reduced capillary/muscle fiber ratio. Moreover, RNase A treatment was associated with a significant reduction in leukocyte infiltration as shown by CD45+ (pan-leukocyte marker), Ly6G+ or MPO+ (neutrophils), MPO+/CitH3+ [neutrophil extracellular traps (NETs)], and CD68+ (macrophages) staining. CD68/MRC1 double staining revealed that RNase A treated mice showed a reduced percentage of M1-like polarized (CD68+/MRC1−) macrophages whereas the percentage of M2-like polarized (CD68+/MRC1+) macrophages was increased.Conclusion: In contrast to RNase 5, RNase A interferes with angiogenesis, which is linked to reduced leukocyte infiltration and NET formation.https://www.frontiersin.org/articles/10.3389/fphys.2020.576736/fullangiogenesiscapillary sproutingRNase ARNase 5extracellular RNAleukocyte recruitment |
| spellingShingle | Manuel Lasch Manuel Lasch Manuel Lasch Konda Kumaraswami Konda Kumaraswami Simona Nasiscionyte Susanna Kircher Susanna Kircher Dominic van den Heuvel Sarah Meister Hellen Ishikawa-Ankerhold Hellen Ishikawa-Ankerhold Elisabeth Deindl Elisabeth Deindl RNase A Treatment Interferes With Leukocyte Recruitment, Neutrophil Extracellular Trap Formation, and Angiogenesis in Ischemic Muscle Tissue Frontiers in Physiology angiogenesis capillary sprouting RNase A RNase 5 extracellular RNA leukocyte recruitment |
| title | RNase A Treatment Interferes With Leukocyte Recruitment, Neutrophil Extracellular Trap Formation, and Angiogenesis in Ischemic Muscle Tissue |
| title_full | RNase A Treatment Interferes With Leukocyte Recruitment, Neutrophil Extracellular Trap Formation, and Angiogenesis in Ischemic Muscle Tissue |
| title_fullStr | RNase A Treatment Interferes With Leukocyte Recruitment, Neutrophil Extracellular Trap Formation, and Angiogenesis in Ischemic Muscle Tissue |
| title_full_unstemmed | RNase A Treatment Interferes With Leukocyte Recruitment, Neutrophil Extracellular Trap Formation, and Angiogenesis in Ischemic Muscle Tissue |
| title_short | RNase A Treatment Interferes With Leukocyte Recruitment, Neutrophil Extracellular Trap Formation, and Angiogenesis in Ischemic Muscle Tissue |
| title_sort | rnase a treatment interferes with leukocyte recruitment neutrophil extracellular trap formation and angiogenesis in ischemic muscle tissue |
| topic | angiogenesis capillary sprouting RNase A RNase 5 extracellular RNA leukocyte recruitment |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2020.576736/full |
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