ß-adrenergic stimulation increases macrophage CD14 expression and E. coli phagocytosis through PKA signaling mechanisms.
CD14 is a glycoprotein that binds bacterial LPS in MØ. It is an essential component of the phagocytic system and is increased in septic shock. Critical injury and sepsis result in elevated endogenous CA levels. CAs have a significant impact on MØ inflammatory functions. We tested the hypothesis that β-adrenergic stimulation regulates CD14 expression and bacterial phagocytosis in BMØ. Murine BMØ stimulated with isoproterenol (>8 h) induced a dose-dependent increase in cell surface CD14 expression. Specific PKA inhibitor (H-89) and gene-silencing (siRNA) studies demonstrated the role of cAMP-dependent PKA in mediating this response. In addition, we observed a correlation between an isoproterenol-mediated increase in CD14 expression and live Escherichia coli uptake in BMØ. Further, the essential role of CD14 in an isoproterenol-mediated increase in E. coli uptake was highlighted from experiments using CD14(-/-) mice. Moreover, the dose response of isoproterenol stimulation to CD14 expression and E. coli phagocytosis overlapped with similar EC50. Additionally, isoproterenol-mediated E. coli phagocytosis was prevented by H-89, suggesting that β-adrenergic stimulus in BMØ increases CD14 expression and live E. coli phagocytosis through a common signaling pathway. Our studies indicate the potential impact of β-adrenergic agents on important innate immune functions.
Muthu
Kuzhali
K
Department of Surgery, Loyola University Medical Center, Maywood, IL 60153, USA. kmuthu@lumc.edu
He
Li-K
LK
Szilagyi
Andrea
A
Strotmon
Patrick
P
Gamelli
Richard L
RL
Shankar
Ravi
R
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002469:Cell Separation; D017868:Cyclic AMP-Dependent Protein Kinases / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli; D005434:Flow Cytometry; D007545:Isoproterenol / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis* / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000276:immunology*; D014162:Transfection
D000318:Adrenergic beta-Agonists; D018950:Lipopolysaccharide Receptors; D034741:RNA, Small Interfering; D017868:Cyclic AMP-Dependent Protein Kinases; D007545:Isoproterenol