Strain-dependent inhibitory effect of mutant mi-MITF on cytotoxic activities of cultured mast cells and natural killer cells of mice

Abstract

MITF is a transcription factor encoded by the mi locus. MITF encoded by mi and Mi or mutant alleles (mi-MITF and Mi or-MITF, respectively) possessed an inhibitory effect, whereas the tg, mi ew and mi ce were null mutants. We examined the cytotoxic activities of cultured mast cells (CMCs) and natural killer (NK) cells of various MITF mutants in C57BL/6 (B6) background. Cytotoxic activities of CMCs and NK cells of B6-mi/mi and B6-Mi or /Mi or mice were remarkably reduced. In B6-tg/tg, B6-mi ew /mi ew and B6-mi ce /mi ce mice, however, the cytotoxic activity of CMCs was reduced only slightly and the NK activity was normal. The cytotoxic activity of CMCs paralleled with the expression level of granzyme B (Gr B) mRNA, and the NK activity with that of perforin (Pfn) mRNA. In contrast to the case of B6-mi/mi mice, cytotoxic activities of CMCs and NK cells were not impaired in WB-mi/mi mice. The expression of Gr B mRNA was not reduced in CMCs of WB-mi/mi mice, and that of Pfn mRNA was not reduced in NK cells of WB-mi/mi mice. WB-mi/mi mice appeared to have factor(s) compensating for the inhibitory effect of mi-MITF on the expression of Gr B and Pfn genes.

Granzyme B is expressed in mouse mast cells in vivo and in vitro and causes delayed cell death independent of perforin

“…1 Recent work on mouse has identified transcripts for the serine proteinase granzyme (gzm) B in cultured naive mast cells. 4 However, protein expression of gzmB has not been shown. GzmB together with gzmA and perforin (perf) are key components of the lytic machinery of cytotoxic leukocytes, that is, natural killer (NK) cells and cytotoxic T lymphocytes (CTL) 5 and are released into the immunological synapse formed between NK/CTL and their target cells.…”

Reduced expression of IL-12 receptor β2 and IL-18 receptor α genes in natural killer cells and macrophages derived from B6-mi/mi mice

“…To ensure the survival of B6-mi/mi mice to 6-8 weeks of age, we fed the weaning B6-mi/mi mice with powdered chow. 10 The original stock of VGA-9-tg/ þ mice, in which the mouse vasopressin-Escherichia coli b-galactosidase transgene is integrated at the 5 0 flanking region of the mi gene, 1,2 were kindly provided by Dr H Arnheiter (National Institutes of Health, Bethesda, MD, USA). The integrated transgene was maintained by repeated backcrosses to our own inbred B6 colony.…”

“…18,[22][23][24][25][26][27] The abnormal phenotypes of B6-mi/mi NK cells resemble those of mice that are deficient in IL-12 or IL-18 signaling. [8][9][10]18,[22][23][24][25][26][27] The administration of IL-12 or IL-18 did not recover the decreased NK activity of B6-mi/mi mice (our unpublished data). In this study, we examined the expression of IL-12Rb1, IL12Rb2, IL-18Ra and IL-18Rb in NK cells that were derived from B6-þ / þ , B6-mi/mi, or B6-tg/tg mice.…”

“…1,2,[5][6][7] These mice are distinguishable from each other in the following respect; B6-mi/mi mice showed, but B6-tg/tg mice do not show abnormal phenotypes of the NK cell and macrophage lineage. [8][9][10][11][12][13] Both B6-mi/ mi and B6-tg/tg mice showed normal NK 1.1 þ cell development, but only B6-mi/mi mice showed impaired NK activity. [8][9][10] Both B6-mi/mi and B6-tg/ tg mice showed normal distributions of osteoclasts, whereas only B6-mi/mi mice showed osteopetrosis, which results from the impaired bone-resorption abilities of their osteoclasts.…”

“…[8][9][10][11][12][13] Both B6-mi/ mi and B6-tg/tg mice showed normal NK 1.1 þ cell development, but only B6-mi/mi mice showed impaired NK activity. [8][9][10] Both B6-mi/mi and B6-tg/ tg mice showed normal distributions of osteoclasts, whereas only B6-mi/mi mice showed osteopetrosis, which results from the impaired bone-resorption abilities of their osteoclasts. 11,12 In addition to the osteoclasts, the peritoneal macrophages of B6-mi/mi mice have been reported to show some abnormal phenotypes, such as decreased phagocytic capacity and decreased acid phosphatase activity.…”