Regulation of eosinophil-active cytokine production from human cord blood-derived mast cells.
Human mast cells are multifunctional tissue-dwelling cells that play a crucial role in eosinophil-dependent disorders, such as asthma and parasitic diseases, by the secretion of eosinophil-active mediators. Mast cell-derived cytokines, generated in response to cross-linking of the high-affinity IgE receptor, can regulate eosinophil activation, survival, and chemotaxis. In this study, mast cells generated from human cord blood progenitors (stem cells) were studied for eosinophil-active inflammatory cytokine expression. Cord blood-derived mast cells (CBDMC) expressed typical intracellular scroll granules and microvilli-like structures on their cell surfaces, demonstrated the presence of tryptase, and elaborated prostaglandin D2 (PGD2) after cross-linkage of the high-affinity receptor for IgE (FcepsilonRI). CBDMC expressed tumor necrosis factor-alpha (TNF-alpha) and the eosinophil-active growth factors, interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF) after activation. (IL-1beta greatly enhanced IgE-dependent production of these cytokines in response to FcepsilonRI cross-linkage, suggesting a role for bystander/phagocytic cells in modulating mast cell function. In contrast, interferon-alpha (IFN-alpha) inhibited IL-5 and GM-CSF generation, and the glucocorticoid, dexamethasone (Dex), inhibited production of IL-5 and GM-CSF from CBDMC. A macrophage-mast cell-eosinophil axis may exist in vivo that may be susceptible to pharmacologic manipulation.
Krishnaswamy
Guha
G
Department of Medicine, East Tennessee State University, Johnson City, TN 37614-0622, USA. krishna@etsu.edu
Hall
Kenton
K
Youngberg
George
G
Hossler
Fred
F
Johnson
David
D
Block
William A
WA
Huang
Shau-Ku
SK
Kelley
Jim
J
Chi
David S
DS
D002478:Cells, Cultured; D053818:Chymases; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism*; D005312:Fetal Blood / Q000166:cytology*; D015870:Gene Expression / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000187:drug effects / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007073:Immunoglobulin E / Q000494:pharmacology; D016898:Interferon-alpha / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015848:Interleukin-5 / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008954:Models, Biological; D015230:Prostaglandin D2 / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D053802:Tryptases; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D016898:Interferon-alpha; D007375:Interleukin-1; D015848:Interleukin-5; D017455:Receptors, IgE; D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D012697:Serine Endopeptidases; D053818:Chymases; D053802:Tryptases; D015230:Prostaglandin D2