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

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 ß-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 α(1A)-, α(1B)-, α(1D)-, α(2A)-, α(2C)-, ß(1)-, ß(2)-, and ß(3)-AR mRNA. A prevented fMLP-induced morphological changes of PMN. CONCLUSIONS: Adrenergic agents reduced PMN responses mainly through ß-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.