Ligation of CD23 activates soluble guanylate cyclase in human monocytes via an L-arginine-dependent mechanism.
Transduction through Fc epsilon R2/CD23 was analyzed in normal human monocytes using immunoglobulin E (IgE)-anti-IgE immune complexes (IgE ICs) and monoclonal antibodies (mAbs) to CD23. Anti-CD23 mAb and IgE IC triggered a time-dependent increase in cGMP and cAMP in interleukin-4-preincubated (CD23+) but not in unstimulated (CD23-) monocytes. Maximal cGMP and cAMP accumulations were observed 10 and 20 min, respectively, after the onset of CD23 ligation. The increase in cGMP was inhibited with N omega-monomethyl-L-arginine (L-NMMA), which also partially affected cAMP accumulation. Addition of an anti-CD23 mAb Fab fragment inhibited the IgE IC- and the anti-CD23 mAb-induced cGMP and cAMP accumulation, confirming the engagement of CD23. In addition, IgE IC and anti-CD23 mAb induced, at least in some donors, a production of nitrite that was inhibited in the presence of L-NMMA. Taken together, these findings suggest a possible involvement of the nitric oxide synthase pathway in IgE IC-mediated activation of CD23+ monocytes.
Paul-Eugène
N
N
INSERM U 365, Institut Curie, Paris, France.
Kolb
J P
JP
Sarfati
M
M
Arock
M
M
Ouaaz
F
F
Debré
P
P
Mossalayi
D M
DM
Dugas
B
B
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000936:Antigen-Antibody Complex / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007073:Immunoglobulin E / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000201:enzymology* / Q000502:physiology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D017455:Receptors, IgE / Q000276:immunology / Q000502:physiology*; D019323:omega-N-Methylarginine
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D017455:Receptors, IgE; D015847:Interleukin-4; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007073:Immunoglobulin E; D001120:Arginine; D000242:Cyclic AMP; D006162:Guanylate Cyclase; D006152:Cyclic GMP