Role and modulation of CD16 expression on eosinophils by cytokines and immune complexes.
BACKGROUND
Blood eosinophils express CD16 on their surface when stimulated in vitro with platelet-activating factor or IFNgamma. Transient expression of CD16 is also observed in vivo following aeroallergen challenge of asthmatic subjects. The present work is aimed at evaluating the possible mechanisms modulating eosinophil expression of CD16 and the biological functions of this receptor.


METHODS
First, purified blood eosinophils were incubated with IL-1beta, IL-2, IL-4, IL-5, IL-9 or IL-16, GM-CSF, IFNgamma, eotaxin or 5-oxo-ETE and CD16 expression was measured. Second, the capacity of CD16 to mediate degranulation induced by IgG immune complexes (IC) was evaluated in eosinophils with low and high CD16 expression. Finally, serum allergen-specific IgE and IgG, and total IgE levels were measured at baseline in allergic asthmatics and correlated with changes observed in blood eosinophil CD16 expression (DeltaCD16) following allergen challenge.


RESULTS
Only IFNgamma and IL-2 significantly increased the number of CD16+ eosinophils, respectively, 37 +/- 10% (p = 0.0038) and 38 +/- 8% (p = 0.0006), compared to control, 7 +/- 2%. IgG IC induced degranulation in eosinophils with low and high CD16 expression and monoclonal anti-CD16 and anti-CD32 antibodies inhibited this. IgG IC increased eosinophil CD16 expression (14 +/- 6%, p = 0.0008) and this effect was blocked by pretreatment with anti-CD32 antibodies. DeltaCD16 following allergen challenge correlated with the specific IgG/total IgE ratio (r(2) = 0.41, p = 0.036).


CONCLUSIONS
These data suggest that formation of IgG IC is associated with surface eosinophil CD16 expression in asthma and that CD16 in cooperation with CD32 mediates IC-induced degranulation.
Davoine
Francis
F
Unité de recherche en pneumologie, Centre de recherche de l'Hôpital Laval, Institut universitaire de cardiologie et pneumologie, Université Laval, Québec, Canada.
Labonté
Isabelle
I
Ferland
Claudine
C
Mazer
Bruce
B
Chakir
Jamila
J
Laviolette
Michel
M
D000918:Antibody Specificity / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000378:metabolism / Q000494:pharmacology*; D016525:Antigenic Modulation / Q000502:physiology*; D039741:Antigens, Dermatophagoides / Q000009:adverse effects / Q000494:pharmacology; D001249:Asthma / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001985:Bronchial Provocation Tests; D015550:Cell Degranulation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology*; D004804:Eosinophils / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D007378:Interleukins / Q000378:metabolism / Q000494:pharmacology; D006109:Poaceae / Q000009:adverse effects; D017452:Receptors, IgG / Q000096:biosynthesis*; D013223:Statistics as Topic
D000936:Antigen-Antibody Complex; D039741:Antigens, Dermatophagoides; D015415:Biomarkers; D016207:Cytokines; D007074:Immunoglobulin G; D007378:Interleukins; D017452:Receptors, IgG; D007073:Immunoglobulin E; D007371:Interferon-gamma