Complement C5a Alters the Membrane Potential of Neutrophils during Hemorrhagic Shock
Background. Polymorphonuclear granulocytes (PMN) play a crucial role in host defense. Physiologically, exposure of PMN to the complement activation product C5a results in a protective response against pathogens, whereas in the case of systemic inflammation, excessive C5a substantially impairs neutro...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2018/2052356 |
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| author | David A. C. Messerer Stephanie Denk Karl J. Föhr Rebecca Halbgebauer Christian K. Braun Felix Hönes Julia Harant Michael Fauler Manfred Frick Benedikt L. Nußbaum Peter Radermacher Sebastian Hafner Markus S. Huber-Lang |
| author_facet | David A. C. Messerer Stephanie Denk Karl J. Föhr Rebecca Halbgebauer Christian K. Braun Felix Hönes Julia Harant Michael Fauler Manfred Frick Benedikt L. Nußbaum Peter Radermacher Sebastian Hafner Markus S. Huber-Lang |
| author_sort | David A. C. Messerer |
| collection | DOAJ |
| description | Background. Polymorphonuclear granulocytes (PMN) play a crucial role in host defense. Physiologically, exposure of PMN to the complement activation product C5a results in a protective response against pathogens, whereas in the case of systemic inflammation, excessive C5a substantially impairs neutrophil functions. To further elucidate the inability of PMN to properly respond to C5a, this study investigates the role of the cellular membrane potential of PMN in response to C5a. Methods. Electrophysiological changes in cellular and mitochondrial membrane potential and intracellular pH of PMN from human healthy volunteers were determined by flow cytometry after exposure to C5a. Furthermore, PMN from male Bretoncelles-Meishan-Willebrand cross-bred pigs before and three hours after severe hemorrhagic shock were analyzed for their electrophysiological response. Results. PMN showed a significant dose- and time-dependent depolarization in response to C5a with a strong response after one minute. The chemotactic peptide fMLP also evoked a significant shift in the membrane potential of PMN. Acidification of the cellular microenvironment significantly enhanced depolarization of PMN. In a clinically relevant model of porcine hemorrhagic shock, the C5a-induced changes in membrane potential of PMN were markedly diminished compared to healthy littermates. Overall, these membrane potential changes may contribute to PMN dysfunction in an inflammatory environment. |
| format | Article |
| id | doaj-art-8748b602bde14a9296c79db7aed0a9e2 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-8748b602bde14a9296c79db7aed0a9e22025-02-03T01:20:49ZengWileyMediators of Inflammation0962-93511466-18612018-01-01201810.1155/2018/20523562052356Complement C5a Alters the Membrane Potential of Neutrophils during Hemorrhagic ShockDavid A. C. Messerer0Stephanie Denk1Karl J. Föhr2Rebecca Halbgebauer3Christian K. Braun4Felix Hönes5Julia Harant6Michael Fauler7Manfred Frick8Benedikt L. Nußbaum9Peter Radermacher10Sebastian Hafner11Markus S. Huber-Lang12Institute of Clinical and Experimental Trauma-Immunology, University Hospital Ulm, 89081 Ulm, GermanyInstitute of Clinical and Experimental Trauma-Immunology, University Hospital Ulm, 89081 Ulm, GermanyDepartment of Anesthesiology, University Hospital Ulm, 89081 Ulm, GermanyInstitute of Clinical and Experimental Trauma-Immunology, University Hospital Ulm, 89081 Ulm, GermanyInstitute of Clinical and Experimental Trauma-Immunology, University Hospital Ulm, 89081 Ulm, GermanyInstitute of Clinical and Experimental Trauma-Immunology, University Hospital Ulm, 89081 Ulm, GermanyInstitute of Clinical and Experimental Trauma-Immunology, University Hospital Ulm, 89081 Ulm, GermanyInstitute of General Physiology, Ulm University, 89081 Ulm, GermanyInstitute of General Physiology, Ulm University, 89081 Ulm, GermanyInstitute of Anesthesiologic Pathophysiology and Method Development, University Hospital Ulm, 89081 Ulm, GermanyInstitute of Anesthesiologic Pathophysiology and Method Development, University Hospital Ulm, 89081 Ulm, GermanyInstitute of Anesthesiologic Pathophysiology and Method Development, University Hospital Ulm, 89081 Ulm, GermanyInstitute of Clinical and Experimental Trauma-Immunology, University Hospital Ulm, 89081 Ulm, GermanyBackground. Polymorphonuclear granulocytes (PMN) play a crucial role in host defense. Physiologically, exposure of PMN to the complement activation product C5a results in a protective response against pathogens, whereas in the case of systemic inflammation, excessive C5a substantially impairs neutrophil functions. To further elucidate the inability of PMN to properly respond to C5a, this study investigates the role of the cellular membrane potential of PMN in response to C5a. Methods. Electrophysiological changes in cellular and mitochondrial membrane potential and intracellular pH of PMN from human healthy volunteers were determined by flow cytometry after exposure to C5a. Furthermore, PMN from male Bretoncelles-Meishan-Willebrand cross-bred pigs before and three hours after severe hemorrhagic shock were analyzed for their electrophysiological response. Results. PMN showed a significant dose- and time-dependent depolarization in response to C5a with a strong response after one minute. The chemotactic peptide fMLP also evoked a significant shift in the membrane potential of PMN. Acidification of the cellular microenvironment significantly enhanced depolarization of PMN. In a clinically relevant model of porcine hemorrhagic shock, the C5a-induced changes in membrane potential of PMN were markedly diminished compared to healthy littermates. Overall, these membrane potential changes may contribute to PMN dysfunction in an inflammatory environment.http://dx.doi.org/10.1155/2018/2052356 |
| spellingShingle | David A. C. Messerer Stephanie Denk Karl J. Föhr Rebecca Halbgebauer Christian K. Braun Felix Hönes Julia Harant Michael Fauler Manfred Frick Benedikt L. Nußbaum Peter Radermacher Sebastian Hafner Markus S. Huber-Lang Complement C5a Alters the Membrane Potential of Neutrophils during Hemorrhagic Shock Mediators of Inflammation |
| title | Complement C5a Alters the Membrane Potential of Neutrophils during Hemorrhagic Shock |
| title_full | Complement C5a Alters the Membrane Potential of Neutrophils during Hemorrhagic Shock |
| title_fullStr | Complement C5a Alters the Membrane Potential of Neutrophils during Hemorrhagic Shock |
| title_full_unstemmed | Complement C5a Alters the Membrane Potential of Neutrophils during Hemorrhagic Shock |
| title_short | Complement C5a Alters the Membrane Potential of Neutrophils during Hemorrhagic Shock |
| title_sort | complement c5a alters the membrane potential of neutrophils during hemorrhagic shock |
| url | http://dx.doi.org/10.1155/2018/2052356 |
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