Interleukin-6 directly modulates stem cell factor-dependent development of human mast cells derived from CD34(+) cord blood cells.
In the present study, we attempted to clarify the effects of interleukin-6 (IL-6) on the growth and properties of human mast cells using cultured mast cells selectively generated by stem cell factor (SCF) from CD34(+) cord blood cells. The addition of IL-6 to cultures containing mast cells resulted in a substantial reduction of the number of progenies grown by SCF in the liquid culture. This IL-6-mediated inhibition of mast cell growth may be due in part to the suppression at the precursor level, according to the results of a clonal cell culture assay. Moreover, a flow cytometric analysis showed that the cultured mast cells grown in the presence of SCF+IL-6 had decreased c-kit expression. The exposure of cultured mast cells to SCF+IL-6 also caused substantial increases in the cell size, frequency of chymase-positive cells, and intracellular histamine level compared with the values obtained with SCF alone. The flow cytometric analysis showed low but significant levels of expression of IL-6 receptor (IL-6R) and gp130 on the cultured mast cells grown with SCF. The addition of either anti-IL-6R antibody or anti-gp130 antibody abrogated the biological functions of IL-6. Although IL-4 exerted an effect similar to that of IL-6 on the cultured mast cells under stimulation with SCF, the results of comparative experiments suggest that the two cytokines use different regulatory mechanisms. Taken together, the present findings suggest that IL-6 modulates SCF-dependent human mast cell development directly via an IL-6R-gp130 system.
Department of Pediatrics, Shinshu University School of Medicine, and Central Clinical Laboratories, Shinshu University Hospital, Matsumoto, Japan.
T
T
Kinoshita
N
N
Sawai
E
E
Hidaka
T
T
Yamashita
K
K
Koike
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000494:pharmacology / Q000502:physiology; D018952:Antigens, CD34 / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D019070:Cell Lineage; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D050822:Cytokine Receptor gp130; D005312:Fetal Blood / Q000166:cytology*; D006131:Growth Inhibitors / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006632:Histamine / Q000096:biosynthesis; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology / Q000494:pharmacology / Q000502:physiology; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018952:Antigens, CD34; D016895:Culture Media, Serum-Free; D006131:Growth Inhibitors; C494199:IL6ST protein, human; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D050822:Cytokine Receptor gp130; D015847:Interleukin-4; D006632:Histamine; D019009:Proto-Oncogene Proteins c-kit