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Adrenergic modulation of migration, CD11b and CD18 expression, ROS and interleukin-8 production by human polymorphonuclear leukocytes

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Abstract

Objectives

Adrenergic modulation of immunity has been extensively characterized, however, few information exist regarding polymorphonuclear leukocytes (PMN), despite their key role in immunity and inflammation. We investigated the effect of adrenergic agents on human PMN migration, CD11b and CD18 expression, reactive oxygen species (ROS) and interleukin (IL)-8 production, and on adrenoceptor (AR) expression.

Methods

Migration was measured by the Boyden chamber assay, CD11b/CD18 expression was assessed by flow cytometry, intracellular ROS were detected by spectrofluorimetry, and IL-8 was quantitated by standard ELISA assay. AR mRNA levels were measured by real-time PCR and PMN morphology was studied by scanning electron microscopy.

Results

Adrenaline(A), noradrenaline and the β-AR agonist isoprenaline reduced N-formyl-Met-Leu-Phe (fMLP)-induced migration, CD11b/CD18 expression, and ROS production, without affecting IL-8. The effect of A on CD11b was antagonized by yohimbine and propranolol, and increased by prazosin. The effect on ROS production was completely abolished by propranolol. PMN expressed α1A-, α1B-, α1D-, α2A-, α2C-, β1-, β2-, and β3-AR mRNA. A prevented fMLP-induced morphological changes of PMN.

Conclusions

Adrenergic agents reduced PMN responses mainly through β-AR, although α-AR may contribute at least to CD11b expression. AR-operated pathways in PMN should be investigated in disease conditions and in the response to therapeutic agents.

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Acknowledgments

AS is developing a research program on the adrenergic modulation of immunity and its role in vascular inflammation and atherosclerosis as part of her work for the PhD Course in Clinical and Experimental Pharmacology, University of Insubria (XXVII Cycle). Part of this study was presented by JD as final thesis for the attainment of the Degree in Medicine and Surgery, University of Insubria, academic year 2013/2014. This work was supported by funds provided by the Center for Research in Medical Pharmacology, University of Insubria. The authors wish to express their gratefulness to Ms. Paola Gervasini, Center for Research in Medical Pharmacology, who was responsible for administration and accounting of the funds.

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Correspondence to Angela Scanzano.

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Responsible Editor: John Di Battista.

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Scanzano, A., Schembri, L., Rasini, E. et al. Adrenergic modulation of migration, CD11b and CD18 expression, ROS and interleukin-8 production by human polymorphonuclear leukocytes. Inflamm. Res. 64, 127–135 (2015). https://doi.org/10.1007/s00011-014-0791-8

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  • DOI: https://doi.org/10.1007/s00011-014-0791-8

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