Beta 2-adrenergic receptor regulation of human neutrophil function is sexually dimorphic.
While the mechanisms underlying the marked sexual dimorphism in inflammatory diseases are not well understood, the sexually dimorphic sympathoadrenal axis profoundly affects the inflammatory response. We tested whether adrenergic receptor-mediated activation of human neutrophil function is sexually dimorphic, since neutrophils provide the first line of defense in the inflammatory response. There was a marked sexual dimorphism in beta(2)-adrenergic receptor binding, using the specific beta(2)-adrenergic receptor ligand, [(3)H]-dihydroalprenolol, with almost three times more binding sites on neutrophils from females (20,878 +/- 2470) compared to males (7331 +/- 3179). There was also a marked sexual dimorphism in the effects of isoprenaline, a beta-adrenergic receptor agonist, which increased nondirected locomotion (chemokinesis) in neutrophils obtained from females, while having no effect on neutrophils from males. Isoprenaline stimulated the release of a chemotactic factor from neutrophils obtained from females, but not from males. This chemotactic factor acts on the G protein-coupled CXC chemokine receptor 2 (CXCR2) chemokine receptor, since an anti-CXCR2 antibody and the selective nonpeptide CXCR2 antagonist SB225002, inhibited chemotaxis produced by this factor. While interleukin- (IL-) 8 is a principal CXCR2 ligand, isoprenaline did not produce an increase in IL-8 release from neutrophils. IL-8-induced chemotaxis was inhibited in a sexually dimorphic manner by isoprenaline, which also stimulated release of a mediator from neutrophils that induced chemotaxis, that was inhibited by anti-CXCR2 antibodies. These findings indicate an important role for adrenergic receptors in the modulation of neutrophil trafficking, which could contribute to sex-differences in the inflammatory response.
Department of Medicine, NIH Pain Center, 521 Parnassus Avenue, San Francisco, CA 94143-0440, USA.
Catherine
C
de Coupade
Robert W
RW
Gear
Paul F
PF
Dazin
Herve Y
HY
Sroussi
Paul G
PG
Green
Jon D
JD
Levine
D058666:Adrenergic beta-2 Receptor Agonists; D000328:Adult; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology*; D012727:Sex Characteristics
D058666:Adrenergic beta-2 Receptor Agonists; D018343:Receptors, Adrenergic, beta-2; D007545:Isoproterenol