NPC 15669 blocks neutrophil CD18 increase and lung injury during cardiopulmonary bypass in pigs
During cardiopulmonary bypass (CPB), neutrophils become activated due to contact with extracorporeal surfaces and binding of complement fragments C3a and C5a, leading to extravasation and subsequent tissue damage. In this study, the effects of the leumedin NPC 15669 (N [9H - (2,7 dimethylfluorenyl -...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
1993-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/S0962935193000201 |
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| _version_ | 1850219299205021696 |
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| author | J. M. Bator A. M. Gillinov K. J. Zehr J. M. Redmond I. C. Wilson A. Herskowitz J. R. Connor R. M. Burch D. E. Cameron |
| author_facet | J. M. Bator A. M. Gillinov K. J. Zehr J. M. Redmond I. C. Wilson A. Herskowitz J. R. Connor R. M. Burch D. E. Cameron |
| author_sort | J. M. Bator |
| collection | DOAJ |
| description | During cardiopulmonary bypass (CPB), neutrophils become activated due to contact with extracorporeal surfaces and binding of complement fragments C3a and C5a, leading to extravasation and subsequent tissue damage. In this study, the effects of the leumedin NPC 15669 (N [9H - (2,7 dimethylfluorenyl - 9 - methoxy) car bonyl]-L-leucine), a leukocyte recruitment inhibitor, were evaluated in a pig model of CPB. NPC 15669 caused significant inhibition of CPB associated increase in CD18 upregulation, lung tissue myeloperoxidase content, and percentage wet weight compared to controls. Lung histology revealed clear airways and minimal neutrophil infiltration in treated animals vs. significant oedema and cellular infiltration in controls. It is concluded that CPB causes a dramatic increase in neutrophil CD18, and that leumedins are effective in inhibiting neutrophil activation and subsequent tissue injury when administered during CPB. |
| format | Article |
| id | doaj-art-7cb7db8933a0477084a993fc12bf377f |
| institution | OA Journals |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 1993-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-7cb7db8933a0477084a993fc12bf377f2025-08-20T02:07:26ZengWileyMediators of Inflammation0962-93511466-18611993-01-012213514110.1155/S0962935193000201NPC 15669 blocks neutrophil CD18 increase and lung injury during cardiopulmonary bypass in pigsJ. M. Bator0A. M. Gillinov1K. J. Zehr2J. M. Redmond3I. C. Wilson4A. Herskowitz5J. R. Connor6R. M. Burch7D. E. Cameron8Scios Nova Inc., 6200 Freeport Centre, Baltimore, MD 21224, USAjohns Hopkins Medical Institution, Department of Cardiac Surgery, Baltimore, MD, USAjohns Hopkins Medical Institution, Department of Cardiac Surgery, Baltimore, MD, USAjohns Hopkins Medical Institution, Department of Cardiac Surgery, Baltimore, MD, USAjohns Hopkins Medical Institution, Department of Cardiac Surgery, Baltimore, MD, USAjohns Hopkins Medical Institution, Division of Cardiology, Dept. of Medicine, Baltimore MD, USAScios Nova Inc., 6200 Freeport Centre, Baltimore, MD 21224, USAScios Nova Inc., 6200 Freeport Centre, Baltimore, MD 21224, USAjohns Hopkins Medical Institution, Department of Cardiac Surgery, Baltimore, MD, USADuring cardiopulmonary bypass (CPB), neutrophils become activated due to contact with extracorporeal surfaces and binding of complement fragments C3a and C5a, leading to extravasation and subsequent tissue damage. In this study, the effects of the leumedin NPC 15669 (N [9H - (2,7 dimethylfluorenyl - 9 - methoxy) car bonyl]-L-leucine), a leukocyte recruitment inhibitor, were evaluated in a pig model of CPB. NPC 15669 caused significant inhibition of CPB associated increase in CD18 upregulation, lung tissue myeloperoxidase content, and percentage wet weight compared to controls. Lung histology revealed clear airways and minimal neutrophil infiltration in treated animals vs. significant oedema and cellular infiltration in controls. It is concluded that CPB causes a dramatic increase in neutrophil CD18, and that leumedins are effective in inhibiting neutrophil activation and subsequent tissue injury when administered during CPB.http://dx.doi.org/10.1155/S0962935193000201 |
| spellingShingle | J. M. Bator A. M. Gillinov K. J. Zehr J. M. Redmond I. C. Wilson A. Herskowitz J. R. Connor R. M. Burch D. E. Cameron NPC 15669 blocks neutrophil CD18 increase and lung injury during cardiopulmonary bypass in pigs Mediators of Inflammation |
| title | NPC 15669 blocks neutrophil CD18 increase and lung injury during cardiopulmonary bypass in pigs |
| title_full | NPC 15669 blocks neutrophil CD18 increase and lung injury during cardiopulmonary bypass in pigs |
| title_fullStr | NPC 15669 blocks neutrophil CD18 increase and lung injury during cardiopulmonary bypass in pigs |
| title_full_unstemmed | NPC 15669 blocks neutrophil CD18 increase and lung injury during cardiopulmonary bypass in pigs |
| title_short | NPC 15669 blocks neutrophil CD18 increase and lung injury during cardiopulmonary bypass in pigs |
| title_sort | npc 15669 blocks neutrophil cd18 increase and lung injury during cardiopulmonary bypass in pigs |
| url | http://dx.doi.org/10.1155/S0962935193000201 |
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