IL-4 and -5 prime human mast cells for different profiles of IgE-dependent cytokine production.
Mast cells (MC) are stem cell factor-dependent tissue-based hematopoietic cells with substantial functional heterogeneity. Cord blood-derived human MC (hMC) express functional receptors for IL-5, and IL-5 mediates stem cell factor-dependent comitogenesis of hMC in vitro. Although IL-5 is not required for normal hMC development, we considered that it might prime hMC for their high-affinity Fc receptor for IgE (FcvarepsilonRI)-dependent generation of cytokines, as previously demonstrated for IL-4. Compared with hMC maintained in stem cell factor alone, hMC primed with IL-5 expressed 2- to 4-fold higher steady-state levels of TNF-alpha, IL-5, IL-13, macrophage inflammatory protein 1alpha, and granulocyte-macrophage colony-stimulating factor transcripts 2 h after FcvarepsilonRI crosslinking and secreted 2- to 5-fold greater quantities of the corresponding cytokines, except IL-13, at 6 h. Unlike IL-4, IL-5 priming did not enhance FcvarepsilonRI-dependent histamine release. Thus, IL-5 augments cytokine production by hMC by a mechanism distinct from that of IL-4 and with a different resultant profile of cytokine production. These observations suggest a potentially autocrine effect of IL-5 on hMC for amplification of allergic immune responses, in addition to its recognized paracrine effects on eosinophils, and implicate both IL-4 and IL-5 in the modulation of the hMC phenotype.
Ochi
H
H
Departments of Medicine and Pediatrics, Harvard Medical School, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA.
De Jesus
N H
NH
Hsieh
F H
FH
Austen
K F
KF
Boyce
J A
JA
D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007073:Immunoglobulin E / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D015848:Interleukin-5 / Q000502:physiology*; D008407:Mast Cells / Q000276:immunology*
D016207:Cytokines; D015848:Interleukin-5; D015847:Interleukin-4; D007073:Immunoglobulin E