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Rabbit polymorphonuclear neutrophils elicit endothelium-dependent contraction in vascular smooth muscle
1Department of Pharmacology, Smith Kline & French Laboratories, King of Prussia, Pennsylvania.
Abstract:
The present studies were designed to investigate the interaction between activated polymorphonuclear neutrophils (PMNs) and endothelial regulation of vascular smooth muscle function. Rabbit peritoneal PMNs (4 x 10(3)-4 x 10(5) cells/ml) added to muscle bath chambers containing phenylephrine-precontracted rabbit isolated aortic rings produced no effect on vascular tone. However, when PMNs were activated with the chemotactic peptide, f-met-leu-phe (0.1 microM), PMNs produced concentration-dependent vascular contraction, which was dependent on the presence of the endothelium. Aortic rings denuded of endothelium were unaffected by activated PMNs. Superoxide dismutase (100 units/ml) treatment of tissues blocked completely PMN-induced vascular contraction, whereas mannitol (20 mM) had no significant effect on PMN-induced vascular contraction. Pyrogallol (a generator of superoxide anion) produced a response that was similar to that observed with activated PMNs. Superoxide anion production was measured separately, and the time of peak rate of superoxide anion production corresponded to the time of the maximal vascular contractile responses. Activated PMNs added to vascular tissues undergoing endothelium-dependent relaxation mediated by either acetylcholine or A23187 produced a reversal of vascular relaxation. Furthermore, activated PMNs did not have any effect on endothelium-independent vascular relaxation produced by either isoproterenol or nitroglycerin. The present investigation reveals that activated PMNs can release superoxide anion and produce endothelium-dependent contraction. The endothelium-dependent contraction may be the result of superoxide anion inactivation of endothelium-derived relaxing factor.
Insights
Activated polymorphonuclear neutrophils (PMNs) release superoxide anion, causing endothelium-dependent vascular contraction. This interaction impacts vascular smooth muscle function by affecting endothelium-derived relaxing factor.
Area of Science:
- Vascular biology
- Immunology
- Cell signaling
Background:
- Polymorphonuclear neutrophils (PMNs) play a role in inflammatory responses.
- Endothelial cells regulate vascular smooth muscle function.
- The interaction between activated immune cells and the vasculature is not fully understood.
Purpose of the Study:
- To investigate the interaction between activated PMNs and endothelial regulation of vascular smooth muscle.
- To determine the role of superoxide anion in PMN-induced vascular effects.
- To elucidate the impact of activated PMNs on endothelium-dependent and -independent relaxation.
Main Methods:
- Isolated rabbit aortic rings were used in muscle bath chambers.
- PMNs were activated using f-met-leu-phe.
- Vascular tone and relaxation were measured in the presence and absence of endothelium.
- Superoxide dismutase and mannitol were used to assess the role of superoxide anion.
- Superoxide anion production was quantified.
Main Results:
- Activated PMNs induced concentration-dependent vascular contraction, dependent on the endothelium.
- Superoxide dismutase blocked PMN-induced contraction, while mannitol had no effect.
- Pyrogallol mimicked the contractile response of activated PMNs.
- Activated PMNs reversed endothelium-dependent relaxation but not endothelium-independent relaxation.
- Peak superoxide anion production correlated with maximal vascular contraction.
Conclusions:
- Activated PMNs release superoxide anion, leading to endothelium-dependent vascular contraction.
- Superoxide anion released by activated PMNs may inactivate endothelium-derived relaxing factor.
- This interaction highlights a mechanism by which immune cells can modulate vascular tone.