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Characterization of the anaphylatoxin inactivator and chemotactic factor inactivator activities during
D L Kreutzer1, J R McCormick, A Despins
1Department of Pathology, Veterans Administration Medical Center, Newington, CT.
Insights
Cardiopulmonary bypass surgery significantly reduces anaphylatoxin inactivator (AI) levels, a key regulator of complement-induced inflammation. This drop in AI activity may contribute to the interstitial edema seen in pump lung syndrome.
Area of Science:
- Immunology
- Cardiovascular Surgery
Background:
- Complement activation generates phlogistic products implicated in pump lung syndrome during cardiopulmonary bypass (CPB).
- Circulating C3a antigens and their vasoactive nature are suspected contributors to interstitial edema and vascular changes in pump lung syndrome.
Purpose of the Study:
- To investigate the impact of CPB and complement activation on serum levels of major regulators for C3a and C5a complement split products.
- To assess the levels of chemotactic factor inactivator (CFI) and anaphylatoxin inactivator (AI) during CPB surgery.
Main Methods:
- Serum samples from patients undergoing CPB were analyzed.
- Levels of anaphylatoxin inactivator (AI) and chemotactic factor inactivator (CFI) were measured.
Main Results:
- A rapid and significant decrease in AI activity was observed within the first 10 minutes of CPB, persisting throughout the procedure.
- AI levels normalized within 24 hours post-surgery.
- CFI levels remained largely stable during and after CPB, with only minimal reductions.
Conclusions:
- The study demonstrates a dramatic depression of AI, a major regulator of complement-derived vasopermeability factors (C3a and C5a), during CPB.
- The reduction in AI activity, potentially linked to carboxypeptidase N, may be a key factor in the interstitial edema associated with pump lung syndrome.
Abstract:
Complement activation productive of phlogistic products has been suggested as one of the major mechanisms of the pump lung syndrome associated with cardiopulmonary bypass (CPB) surgery. Recent studies have demonstrated the presence of circulating C3a antigens in the serum of patients undergoing CPB and have suggested that the vasoactive nature of C3a may contribute directly to the interstitial edema and vascular changes seen in pump lung syndrome. In an effort to unravel the underlying mechanisms of pump lung syndrome, we undertook investigations to determine whether CPB and associated complement activation would alter the serum levels of the major regulators of both C3a and C5a complement split products. These serum regulators designated chemotactic factor inactivator (CFI) and anaphylatoxin inactivator (AI) were measured in the serum of patients undergoing CPB. In these studies, we demonstrated that during CPB a rapid and dramatic drop in the anaphylatoxin inactivator activities occurred within the first 10 minutes of CPB. These lowered AI levels were maintained throughout the CPB but AI levels returned to normal within 24 hours postsurgery. CFI levels were generally maintained throughout the CPB surgery with only minimal depressions in CFI levels during or after CPB surgery. These studies clearly demonstrate that the major regulator system of the complement-derived vasopermeability factors (C3a and C5a) is dramatically depressed during cardiopulmonary bypass and may suggest that the mechanisms of interstitial edema associated with pump lung syndrome may at least, in part, be related to the loss of the serum regulator enzyme carboxypeptidase N, also designated AI.