Human basophils secrete IL-3: evidence of autocrine priming for phenotypic and functional responses in allergic disease.
Although IL-3 is commonly recognized for its growth factor-like activity, in vitro studies have long demonstrated a unique capacity for this cytokine to also augment the proinflammatory properties and phenotype of human basophils. In particular, basophils secrete mediators that are hallmarks in allergic disease, including vasoactive amines (e.g., histamine), lipid metabolites (e.g., leukotriene C(4)), and cytokines (e.g., IL-4/IL-13), which are all markedly enhanced with IL-3 pretreatment. This priming phenomenon is observed in response to both IgE-dependent and IgE-independent stimulation. Additionally, IL-3 directly activates basophils for IL-13 secretion and enhanced CD69 expression, two markers that are elevated in allergic subjects. Lymphocytes are commonly thought to be the source of the IL-3 that primes for these basophil responses. However, we demonstrate herein for the first time that basophils themselves rapidly produce IL-3 (within 4 h) in response to IgE-dependent activation. More importantly, our findings definitively show that basophils rapidly bind and utilize the IL-3 they produce, as evidenced by functional and phenotypic activity that is inhibited in the presence of neutralizing anti-IL-3 receptor (CD123) Abs. We predict that autocrine IL-3 activity resulting from low-level IgE/FcepsilonRI cross-linking by specific allergen represents an important mechanism behind the hyperreactive nature of basophils that has long been observed in allergic disease.
Schroeder
John T
JT
Department of Medicine, Division of Allergy and Clinical Immunology at Johns Hopkins Asthma and Allergy Center, Johns Hopkins University, Baltimore, MD 21224, USA. schray@jhmi.edu
Chichester
Kristin L
KL
Bieneman
Anja P
AP
D000328:Adult; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D019898:Autocrine Communication / Q000276:immunology*; D001491:Basophils / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006632:Histamine / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D007377:Interleukin-3 / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type; D008875:Middle Aged; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D017455:Receptors, IgE / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D006632:Histamine; D007073:Immunoglobulin E; D007377:Interleukin-3; D037181:Lectins, C-Type; D012333:RNA, Messenger; D017455:Receptors, IgE; D000099192:CD69 Antigens; C502447:MS4A2 protein, human