학술논문
α 1B/D -adrenoceptors regulate chemokine receptor-mediated leukocyte migration via formation of heteromeric receptor complexes.
Document Type
Academic Journal
Author
Enten GA; Department of Surgery, Morsani College of Medicine, University of South Florida, Tampa, FL 33612.; Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612.; Gao X; Department of Surgery, Morsani College of Medicine, University of South Florida, Tampa, FL 33612.; Strzelinski HR; Department of Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612.; Weche M; Department of Surgery, Morsani College of Medicine, University of South Florida, Tampa, FL 33612.; Liggett SB; Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612.; Department of Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612.; Majetschak M; Department of Surgery, Morsani College of Medicine, University of South Florida, Tampa, FL 33612.; Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612.
Source
Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
Subject
Language
English
Abstract
It is known that catecholamines regulate innate immune functions. The underlying mechanisms, however, are not well understood. Here we show that at least 20 members of the human chemokine receptor (CR) family heteromerize with one or more members of the α1-adrenergic receptor (AR) family in recombinant systems and that such heteromeric complexes are detectable in human monocytes and the monocytic leukemia cell line THP-1. Ligand binding to α1-ARs inhibited migration toward agonists of the CR heteromerization partners of α1B/D-ARs with high potency and 50 to 77% efficacy but did not affect migration induced by a noninteracting CR. Incomplete siRNA knockdown of α1B/D-ARs in THP-1 cells partially inhibited migration toward agonists of their CR heteromerization partners. Complete α1B-AR knockout via CRISPR-Cas9 gene editing in THP-1 cells (THP-1_ADRA1BKO) resulted in 82% reduction of α1D-AR expression and did not affect CR expression. Migration of THP-1_ADRA1BKO cells toward agonists of CR heteromerization partners of α1B/D-ARs was reduced by 82 to 95%. Our findings indicate that CR:α1B/D-AR heteromers are essential for normal function of CR heteromerization partners, provide a mechanism underlying neuroendocrine control of leukocyte trafficking, and offer opportunities to modulate leukocyte and/or cancer cell trafficking in disease processes.