Differential regulation of mast cell function by IL-10 and stem cell factor.
In the development of rodent mast cells (MC), IL-10 significantly enhances the growth factor activity of stem cell factor (SCF). The differential effects of IL-10 and SCF on function of rat peritoneal MC (PMC) are investigated in this study. IL-10 inhibits both constitutive and Ag-induced nitric oxide production by PMC in a dose-dependent manner, whereas SCF does not affect nitric oxide production by PMC. Short term (20-min) incubation with IL-10 does not affect Ag-induced histamine secretion, whereas long term (24-h) incubation with IL-10 significantly potentiates Ag-induced histamine secretion, an effect similar to those reported for IL-3 and IL-4 in mouse MC. By contrast, SCF significantly potentiates Ag-induced histamine secretion in both short term (20-min) and long term (24-h) experiments. Both constitutive and Ag-induced TNF-alpha production by PMC are dose-dependently inhibited by IL-10, whereas they are not affected by SCF at all doses tested (2-500 ng/ml) and incubation times observed (3-24 h). Interestingly, rat PMC constitutively express IL-10 mRNA and proteins, as tested by reverse transcription-PCR and immunocytochemistry. In addition, it was found by flow cytometry that 23.5% PMC express surface IL-10. Moreover, treatment of PMC with anti-IL-10 Ab for 6 h significantly potentiates constitutive and Ag-induced TNF-alpha production by rat PMC. Thus, IL-10 and SCF exert different regulatory effects on MC secretory function. IL-10 produced by MC has the potential to regulate MC function in an autocrine manner, an effect that may be highly relevant to responses involving MC activation.
Lin
T J
TJ
Department of Medicine, University of Alberta, Edmonton, Canada.
Befus
A D
AD
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D019898:Autocrine Communication / Q000187:drug effects / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D002469:Cell Separation; D006636:Histamine Release / Q000276:immunology; D016753:Interleukin-10 / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology*; D009559:Nippostrongylus / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis; D010529:Peritoneal Cavity / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019089:Stem Cell Factor / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000947:Antigens, Helminth; D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D002118:Calcium