IgE influences the number and function of mature mast cells, but not progenitor recruitment in allergic pulmonary inflammation.
Studies performed using cultured cells indicate that IgE functions not only to trigger degranulation of mast cells following allergen exposure, but also to enhance their survival. Such an influence of IgE on mast cell homeostasis during allergic responses in vivo has not been established. In this study, we show that inhalation of Aspergillus fumigatus extract in mice induced a dramatic rise in IgE accompanied by an increase in airway mast cells. These had an activated phenotype with high levels of FcepsilonRI. Plasma mast cell protease-1 was also increased, indicating an elevated systemic mast cell load. In addition, enhanced levels of IL-5 and eosinophils were observed in the airway. Both mast cell expansion and activation were markedly attenuated in IgE(-/-) animals that are incapable of producing IgE in response to A. fumigatus. The recruitment of eosinophils to the airways was also reduced in IgE(-/-) mice. Analyses of potential cellular targets of IgE revealed that IgE Abs are not required for the induction of mast cell progenitors in response to allergen, but rather act by sustaining the survival of mature mast cells. Our results identify an important role for IgE Abs in promoting mast cell expansion during allergic responses in vivo.
Mathias
Clinton B
CB
Division of Immunology, Children's Hospital, Boston, MA 02115, USA.
Freyschmidt
Eva-Jasmin
EJ
Caplan
Benjamin
B
Jones
Tatiana
T
Poddighe
Dimitri
D
Xing
Wei
W
Harrison
Krista L
KL
Gurish
Michael F
MF
Oettgen
Hans C
HC
D019264:Adoptive Transfer; D000818:Animals; D001232:Aspergillus fumigatus / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D053818:Chymases / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000276:immunology; D005434:Flow Cytometry; D006706:Homeostasis / Q000276:immunology; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism; D007073:Immunoglobulin E / Q000276:immunology*; D015848:Interleukin-5 / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D017455:Receptors, IgE / Q000276:immunology / Q000378:metabolism; D013234:Stem Cells / Q000276:immunology* / Q000378:metabolism
D015848:Interleukin-5; C502447:MS4A2 protein, human; D017455:Receptors, IgE; D007073:Immunoglobulin E; D053818:Chymases; C509230:Mcpt1 protein, mouse