IL-4 and IgE-anti-IgE modulation of 15(S)-hydroxyeicosatetraenoic acid release by mononuclear phagocytes.
BACKGROUND
IL-4 modulates the synthesis of IgE, the expression of CD23, and the release of 15(S)-hydroxyeicosatetraenoic (15[S]-HETE).


OBJECTIVE
We evaluated the release of 15(S)-HETE by IL-4-stimulated monocytes and verified whether the observed increase in 15(S)-HETE release after passive sensitization and anti-IgE challenge of IL-4-treated monocytes was secondary to an increased CD23 expression.


METHODS
Human monocytes were incubated for 24, 48, and 72 hours with IL-4 (10 ng/mL) with or without an IgE-anti-IgE stimulation. We evaluated CD23 expression by immunocytochemistry and 15(S)-HETE release by HPLC and RIA. To prove that the increase in 15(S)-HETE release was due to the effect of IL-4 on CD23, we performed experiments with an anti-CD23 blocking mAb.


RESULTS
CD23 expression and 15(S)-HETE release were significantly increased by IL-4, reaching a peak after 72 hours (P <.02). After passive sensitization with human IgE and anti-IgE challenge, IL-4-stimulated monocytes released higher amounts of 15(S)-HETE than IL-4-unstimulated monocytes (P <.02). Pretreatment with the anti-human B-cell CD23 MHM6 mAb caused a dose-dependent inhibition of 15(S)-HETE release.


CONCLUSIONS
This study shows that immunologic challenge of IL-4-treated, passively sensitized monocytes results in a CD23-dependent additional increase of 15(S)-HETE release, indicating the presence of a synergistic effect of IL-4 on CD23 expression and 15(S)-HETE production.
Profita
M
M
Istituto di Fisiopatologia Respiratoria, C.N.R., Palermo, Italy.
Vignola
A M
AM
Mirabella
A
A
Siena
L
L
Sala
A
A
Gjomarkaj
M
M
Bousquet
J
J
Bonsignore
G
G
D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000494:pharmacology*; D001249:Asthma / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D007073:Immunoglobulin E / Q000276:immunology; D015847:Interleukin-4 / Q000494:pharmacology*; D009000:Monocytes / Q000276:immunology; D010586:Phagocytes / Q000187:drug effects / Q000378:metabolism*; D017455:Receptors, IgE / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D000888:Antibodies, Anti-Idiotypic; D000936:Antigen-Antibody Complex; D006893:Hydroxyeicosatetraenoic Acids; D017455:Receptors, IgE; C026408:anti-IgE antibodies; D015847:Interleukin-4; D007073:Immunoglobulin E; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid