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Functional and phenotypic changes in polymorphonuclear neutrophils induced by catecholamines
B Trabold1, M Gruber, D Fröhlich
1Department of Anaesthesiology, University of Regensburg, Regensburg, Germany. benedikt.trabold@klinik.uni-regensburg.de
Purpose:
To elucidate differential functional and phenotypic changes in response to relevant catecholamines, the generation of oxidative free radicals by PMN, and changes in the expression of L-selectin and Mac-1 on the surface of PMN were examined in the presence of epinephrine, norepinephrine and dopamine in physiological and pharmacological concentrations.
Materials And Methods:
Human polymorphonuclear neutrophils were obtained from healthy donors and pretreated with 0.5 nM or 500 nM epinephrine; 1.18 nM or 1 180 nM norepinephrine; or 0.26 nM or 261 nM dopamine, followed by stimulation with FMLP. Stimulated neutrophils were incubated with antibodies against CD 11 b or CD 62 l and assessed by flow cytometry. Additional probes were assessed by flow cytometry for the generation of oxidative free radicals.
Results:
All catecholamines in high concentration inhibited the suppression of CD 62 l expression and CD 11 b upregulation following stimulation with FMLP. A high concentration of epinephrine suppresses generation of oxidative free radicals.
Conclusions:
The effect of catecholamines on the expression of CD 62 l explains the increased expression of L-selection on PMN observed after trauma. The suppression of CD 11 b reduces leukocyte adherence and consecutive abnormalities in microvascular flow. Epinephrine inhibits the generation of oxidative free radicals by PMN with potentially detrimental effects with respect to bacterial clearance.
Insights
High concentrations of catecholamines like epinephrine, norepinephrine, and dopamine affect polymorphonuclear neutrophils (PMN). Epinephrine specifically inhibits PMN oxidative free radical generation, impacting bacterial clearance.
Area of Science:
- Immunology
- Pharmacology
- Cell Biology
Background:
- Polymorphonuclear neutrophils (PMN) play a critical role in the immune response.
- Catecholamines, such as epinephrine, norepinephrine, and dopamine, are involved in various physiological processes.
- Understanding catecholamine effects on PMN function is crucial for managing inflammatory and immune responses.
Purpose of the Study:
- To investigate how epinephrine, norepinephrine, and dopamine influence PMN functional and phenotypic changes.
- To examine the generation of oxidative free radicals by PMN under catecholamine influence.
- To assess changes in L-selectin (CD 62 l) and Mac-1 (CD 11 b) expression on PMN surfaces.
Main Methods:
- Human PMN were isolated from healthy donors.
- PMN were pretreated with varying concentrations of epinephrine, norepinephrine, or dopamine.
- Cells were stimulated with FMLP, and surface marker expression (CD 11 b, CD 62 l) was analyzed via flow cytometry.
- Oxidative free radical generation was also assessed using flow cytometry.
Main Results:
- High concentrations of all tested catecholamines inhibited the FMLP-induced suppression of CD 62 l expression.
- High concentrations of all tested catecholamines inhibited FMLP-induced CD 11 b upregulation.
- High-dose epinephrine specifically suppressed the generation of oxidative free radicals by PMN.
Conclusions:
- Catecholamine-mediated effects on CD 62 l expression may explain increased L-selectin on PMN post-trauma.
- Suppression of CD 11 b by catecholamines can reduce leukocyte adherence and microvascular flow abnormalities.
- Epinephrine's inhibition of PMN oxidative free radical generation may have detrimental effects on bacterial clearance.
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