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The complement regulators C1 inhibitor and soluble complement receptor 1 attenuate acute lung injury in rabbits
1Department of Anaesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, Dresden, Germany.
Abstract:
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.
Insights
Complement inhibitors C1 inhibitor and soluble complement receptor 1 significantly reduced pulmonary edema and artery pressure in acute lung injury models. These findings highlight the protective effects of complement inhibition in lung injury.
Area of Science:
- Immunology
- Pulmonary Medicine
- Pharmacology
Background:
- Complement system activation is a key factor in acute lung injury pathogenesis.
- Specific complement inhibitors offer a promising therapeutic avenue for acute lung injury.
Purpose of the Study:
- To investigate the therapeutic impact of C1 inhibitor and soluble complement receptor 1 on pulmonary edema and pulmonary artery pressure in acute complement-induced lung injury.
Main Methods:
- Isolated perfused rabbit lungs were exposed to normal human serum (NHS) to induce lung injury.
- Complement activation was blocked using C1 inhibitor or soluble complement receptor 1.
- Pulmonary artery pressure and lung weight gain were continuously monitored.
Main Results:
- NHS administration significantly increased pulmonary artery pressure and caused edema.
- Both C1 inhibitor and soluble complement receptor 1 significantly attenuated the increase in pulmonary artery pressure and reduced edema formation.
- Inhibitors also decreased thromboxane release and deposition of C3c and C5b-9.
Conclusions:
- C1 inhibitor and soluble complement receptor 1 effectively reduce complement-induced pulmonary capillary leakage and pulmonary artery pressure.
- Complement inhibition demonstrates a protective effect in isolated perfused rabbit lungs experiencing acute lung injury.