IL-4 enhances proliferation and mediator release in mature human mast cells.
Tissue mast cells (MC) are recognized as key effector cells of immediate-type allergic reactions releasing inflammatory mediators and cytokines on stimulation with antigen, but they also might be involved in IgE-independent inflammatory and tissue repair processes. The mechanism of human MC regulation in tissue is not fully understood. Here, we show that IL-4, in synergy with stem cell factor (SCF), regulates the function of purified human MC isolated from intestinal tissue. Whereas SCF induced only marginal proliferation of MC cultured in vitro up to 4 weeks, addition of IL-4 and SCF strongly increased the proliferation rate. Moreover, IL-4, which by itself had no visible effect on human MC, enhanced the release of histamine, leukotriene C4, and IL-5 in MC triggered by IgE receptor crosslinking. The IL-4 effects occurred in a dose-dependent fashion (ED50 = 100 pg/ml) and could be totally blocked by a competitive IL-4 receptor antagonist. Our data indicate that IL-4 is an important regulator of human MC function and suggest that mature MC retain the capacity to proliferate in a particular tissue environment.
Department of Gastroenterology and Hepatology, Medical School of Hannover, D-30623 Hannover, Germany. bischoff.stephan@mh-hannover.de
S C
SC
Bischoff
G
G
Sellge
A
A
Lorentz
W
W
Sebald
R
R
Raab
M P
MP
Manns
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics*; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000235:genetics; D007422:Intestines / Q000276:immunology; D007700:Kinetics; D017997:Leukotriene C4 / Q000096:biosynthesis; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019089:Stem Cell Factor / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016207:Cytokines; D015848:Interleukin-5; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D017997:Leukotriene C4