IgE(+), Kit(-), I-A/I-E(-) myeloid cells are the initial source of Il-4 after antigen challenge in a mouse model of allergic pulmonary inflammation.
BACKGROUND
IL-4 is generated within hours after antigen lung challenge and influences events that take place early in the induction of pulmonary inflammation. However, the cells responsible for this early IL-4 production in the lung are unknown.


OBJECTIVE
We sought to characterize the initial inflammatory events in the lung after antigen challenge and to identify cells responsible for producing IL-4 at early time points.


METHODS
Mice were sensitized with ovalbumin or passive IgE and challenged intranasally. Histologic measures of inflammation were used, and lung tissue cytokine production was analyzed by means of RT-PCR. Cells producing IL-4 were characterized by means of in situ hybridization and flow cytometry.


RESULTS
IL-4 mRNA was detectable 100 minutes after challenge in sensitized animals. Blockade of this early IL-4 downregulated vascular cell adhesion molecule 1 mRNA expression and attenuated the early recruitment of eosinophils to the lung. CD4-depleted and mast cell-deficient mice both expressed early IL-4. Cellular analysis revealed the presence of IL-4 protein at 100 minutes exclusively in IgE(+) myeloid cells that did not express CD3, Kit, or I-A/I-E. Moreover, IL-4 production induced by means of passive IgE sensitization and abrogated in FcR gamma-chain-deficient mice supports the conclusion that this IL-4 production is dependent on IgE/gamma-chain interaction.


CONCLUSIONS
IL-4 production by an IgE/gamma-chain-dependent mechanism occurs rapidly after allergen challenge. At these early time points, IL-4 is produced by a myeloid cell with the characteristics of a mouse basophil (IgE(+), Kit(-), I-A/I-E(-)). These data thus suggest that strategies targeting basophils should be considered in the treatment of early lung inflammation.
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852, USA.
Stefano
S
Luccioli
Dan T
DT
Brody
Syed
S
Hasan
Andrea
A
Keane-Myers
Calman
C
Prussin
Dean D
DD
Metcalfe
D000281:Administration, Intranasal; D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology; D001491:Basophils / Q000276:immunology; D004195:Disease Models, Animal; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007249:Inflammation / Q000209:etiology / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis*; D008168:Lung / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis; D011961:Receptors, Fc / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000209:etiology / Q000276:immunology*
D000941:Antigens; D000949:Histocompatibility Antigens Class II; D011961:Receptors, Fc; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin; D019009:Proto-Oncogene Proteins c-kit