Mechanisms of strain-dependent development of mast cells from mouse splenocytes.
Mast cell development from spleen cells was not triggered by prostaglandin E1 (PGE1) or dibutyryl cAMP (db-cAMP) during a 12 day culture when the spleen cells were obtained from C57BL/6N and DBA/1 mice, but mast cells did develop when the spleen cells were obtained from C3H/HeN, BALB/c and ICR mice. A lack of endogenous IFN-gamma in the initial 2 days of the culture period was responsible for the failure. This was confirmed by adding neutralizing anti-IFN-gamma antibody and rIFN-gamma to the cultures and by determining IFN-gamma levels in the spleen cell cultures. Th1 cells in the spleens of C57Bl and DBA/1 mice were much more sensitive to PGE1 and db-cAMP than Th1 cells from other inbred mice strains, and consequently, IFN-gamma production was inhibited in spleen cell cultures of C57BL and DBA/1 mice on addition of PGE1 or db-cAMP. Furthermore, the different sensitivities of Th1 cells to PGE and db-cAMP were dependent on the different levels of IL-12 p40 monomers or homodimers in the spleen cell cultures. As the endogenous specific inhibitors of IL-12 p70 (heterodimers of p40 and p35), large amounts of IL-12 p40 monomers or homodimers in the spleen cell cultures of C57BL and DBA/1 mice enhanced the ability of PGE1 and db-cAMP to inhibit IFN-gamma production by antagonizing the activity of IL-12 heterodimers. These results indicate that the strain-dependent development of mast cells from mouse splenocytes is related to endogenous IFN-gamma levels, which are regulated by PGE, db-cAMP, IL-12 p70 and IL-12 p40.
Hu
Zhi-Qing
ZQ
Department of Microbiology and Immunology, Showa Univrsity School of Medicine, Tokyo, Japan. zqhu@med.showa-u.ac.jp
Zhao
Wei-Hua
WH
Shimamura
Tadakatsu
T
D000527:Alprostadil / Q000276:immunology / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000276:immunology / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D005343:Fibrinolytic Agents / Q000276:immunology / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D013045:Species Specificity; D013154:Spleen / Q000166:cytology / Q000276:immunology*
D016207:Cytokines; D005343:Fibrinolytic Agents; D003994:Bucladesine; D000527:Alprostadil