CD23 and allergic pulmonary inflammation: potential role as an inhibitor.
CD23, a receptor for immunoglobulin E, is expressed at increased levels in asthmatic and atopic individuals and has been associated with disorders characterized by chronic inflammation. Using an established murine model, we employed several complementary strategies to investigate the role of CD23 in allergic pulmonary inflammation and airway hyperresponsiveness (AHR). Specifically, these approaches included the modulation of CD23 function in vivo by administration of anti-CD23 monoclonal antibody (mAb) or Fab fragments to wild-type mice and the analysis of CD23-deficient mice. Administration of anti-CD23 mAb, but not anti-CD23 Fab fragments, produced attenuation of pulmonary inflammation, AHR, and CD8(+) T-cell activation. On the basis of a model that the anti-CD23 mAb transduces, whereas the Fab fragment inhibits, CD23 signaling, these results suggest that CD23 negatively regulates pulmonary inflammation and AHR. This hypothesis is supported by our observation that CD23-deficient mice developed increased inflammation and AHR after sensitization and challenge with allergen. Together, these results indicate that CD23 negatively regulates pulmonary inflammation and airway hyperreactivity.
Cernadas
M
M
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
De Sanctis
G T
GT
Krinzman
S J
SJ
Mark
D A
DA
Donovan
C E
CE
Listman
J A
JA
Kobzik
L
L
Kikutani
H
H
Christiani
D C
DC
Perkins
D L
DL
Finn
P W
PW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D017455:Receptors, IgE / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D017455:Receptors, IgE; D007073:Immunoglobulin E; D010047:Ovalbumin