The complement regulators C1 inhibitor and soluble complement receptor 1 attenuate acute lung injury in rabbits
Because activation of the complement system plays a major role in the pathogenesis of acute lung injury, the availability of new specific complement inhibitors represents a promising therapeutic approach. In the present study we investigated pulmonary edema formation and pulmonary artery pressure (P...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2000
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| In: |
Shock
Year: 2000, Volume: 13, Issue: 4, Pages: 285-290 |
| ISSN: | 1540-0514 |
| DOI: | 10.1097/00024382-200004000-00006 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1097/00024382-200004000-00006
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| Author Notes: | A. Heller, M. Kunz, A. Samakas, M. Haase, M. Kirschfink, T. Koch |
| Summary: | Because activation of the complement system plays a major role in the pathogenesis of acute lung injury, the availability of new specific complement inhibitors represents a promising therapeutic approach. In the present study we investigated pulmonary edema formation and pulmonary artery pressure (PAP) in acute complement-induced lung injury for possible therapeutic impact of the complement regulators C1 inhibitor and soluble complement receptor 1. Eighteen isolated and ventilated rabbit lungs were perfused with pooled normal human serum (NHS, final concentration 35%) in Krebs-Henseleit buffer in a recirculating system. Lung weight gain and PAP were continuously recorded. Complement activation was blocked by the addition of C1 inhibitor (1.0 U/mL, n = 6) or sCR 1 (2.0 microg/mL, n = 6). Lungs that received NHS without inhibitors served as controls (n = 6). This study was performed according to the Helsinki Declaration and approved by the local government. Application of NHS resulted in an increase of PAP within 20 min from 8+/-2 to 42+/-6 mmHg, which was significantly (P < 0.05) decreased by C1-Inh (25+/-5 mmHg) and sCRI (20 +/-3 mmHg). Moreover, pulmonary edema formation after NHS, as assessed by overall weight gain, was reduced by both C1-Inh and sCR1, compared with controls. These findings were paralleled with significantly decreased thromboxane release rates and reduced tissue deposition of C3c and C5b-9. C1 inhibitor and sCR1 attenuate the complement-induced pulmonary capillary leakage and PAP increase, indicating the protective effect of complement inhibition in isolated perfused rabbit lungs. |
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| Item Description: | Gesehen am 17.02.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1540-0514 |
| DOI: | 10.1097/00024382-200004000-00006 |