Related Experiment Videos
C5a-induced myocardial ischemia: role for CD18-dependent PMN localization and PMN-platelet interactions
M P Fletcher1, G L Stahl, J C Longhurst
1Department of Internal Medicine, University of California, Davis 95616.
The American Journal of Physiology
|November 1, 1993
Summary
Complement component 5a (C5a) triggers myocardial ischemia via thromboxane A2 (TxA2) and granulocyte (PMN) interactions. Blocking CD18 on PMNs with IB4 inhibits these C5a-induced effects, suggesting a therapeutic target.
Area of Science:
- Cardiovascular Research
- Immunology
- Hematology
Background:
- Intracoronary C5a in swine reduces coronary blood flow and myocardial function.
- These effects are linked to thromboxane A2 (TxA2)-induced vasoconstriction and granulocyte (PMN) sequestration.
- The origin of TxA2 and the role of CD18-dependent PMN function in this process require clarification.
Purpose of the Study:
- To determine the source of TxA2 production in response to C5a.
- To investigate the role of CD18-dependent PMN function in C5a-mediated myocardial ischemia.
- To evaluate the efficacy of an anti-CD18 monoclonal antibody (IB4) in blocking these responses.
Main Methods:
- Isolated C5a-stimulated porcine PMNs and platelets were analyzed for TxB2 production.
- An anti-CD18 monoclonal antibody (IB4) was used to block CD18 function on PMNs.
- In vivo studies in swine assessed the effects of IB4 on arterial blood pressure, platelet counts, PMN counts, coronary blood flow, and myocardial segment shortening following C5a administration.
Main Results:
- C5a-stimulated PMNs and platelets, but not isolated cells, produced TxB2, indicating a synergistic interaction.
- IB4 bound to porcine PMN CD18 and inhibited C5a-induced PMN functions.
- In vivo, IB4 administration ameliorated C5a-induced decreases in PMN count, coronary blood flow, and segment shortening, despite transiently affecting blood pressure and platelet counts.
Conclusions:
- TxB2 production in response to C5a is mediated by a PMN-platelet interaction.
- IB4 effectively blocks CD18 on porcine PMNs, inhibiting C5a-induced PMN functions.
- CD18-dependent PMN sequestration plays a significant role in C5a-induced myocardial ischemia, suggesting PMN-platelet interactions as a therapeutic target.