Disease relevance of Gzmc

• Nonsuppurative destructive cholangitis (NSDC), a process of T-cell-mediated destruction of biliary epithelia observed in primary biliary cirrhosis (PBC), graft-versus-host disease (GVHD), and hepatic allograft rejection (HAR), also occurs in the B10 [1].
• Analysis of B10 recombinant mice showed that the Dd allele (in B10.A(5R) mice) prevented CD8+ T cell accumulation in the lung, resulting in intense lung eosinophilia [2].
• Although both C57BL/10 (B10) and BALB/c mice bear the susceptible phenotype of innate resistance, Calmette-Guérin bacillus (BCG) vaccination generated efficient API in B10 but not in BALB/c mice [3].
• Immunogenicity and protective efficacy of a DNA vaccine encoding Ag85A from Mycobacterium tuberculosis were compared in BALB/c and C57BL (B6 and B10) mice immunized by intramuscular (i.m.) needle injection or epidermal gene gun (gg) bombardment [4].
• The mutant toxin did not cause weight loss in B10 [5].

Psychiatry related information on Gzmc

• At 1 h post-training, both contextual and cued fear memory deficits were more widespread: all strains except for B6 and B10 showed impairments of both types of memory [6].

High impact information on Gzmc

• In this study we started with a peptide that was immunogenic in B10 mice; it was thus known to be able to interact with the MHC molecule, and T cells existed which could recognise the peptide-MHC complex [7].
• Here we present evidence that individual male mice (B10) made tolerant to two different H-2 haplotypes (B10.BR, B10.D2) can transmit the tolerance state to each haplotype independently, yet often simultaneously, at a high frequency to both first and second generation progeny [8].
• In contrast, donor cells could not be propagated from the bone marrow or other lymphoid tissues of nonimmunosuppressed C3H mice rejecting cardiac allografts from the same donor strain (B10) [9].
• Further evidence that the GM-CSF-stimulated class IIdim or class II-depleted hepatic NPC were immature DC was obtained by injecting them into allogeneic B10 (H-2b I-E-) recipients [10].
• To examine the effect of H-2a expressed only on radioresistant host elements, we prepared fully allogeneic chimeras by administering B10 bone marrow to lethally irradiated B10.A recipients [11].

Chemical compound and disease context of Gzmc

• Among the various B10 and C3H strains, significant differences in the development of diabetes (hyperglycemia) are noted demonstrating that genes within the H-2 complex influence the susceptibility to the diabetogenic effect of low-dose streptozotocin treatment [12].
• Clone B10, specific for the viral coat m.w. 70,000 glycoprotein, could be rapidly activated in situ after local transfer with intact tumor cells in syngeneic hosts to produce a delayed-type hypersensitivity reaction [13].
• Congenic and double congenic mice expressing different H-7 alleles with varying H-2 haplotypes on the C57BL/10 (B10) background were tested for their susceptibility to Friend virus (FV) infection [14].
• The 65-kDa stress protein from Mycobacterium bovis (Bacillus Calmette Guérin) elicited T cell proliferation and antibody responses in seven B10 congenic mouse strains with different H-2 haplotypes [15].
• To determine the locus in the H-2 complex that affects susceptibility to the development of pulmonary adenomas in mice, H-2 congenic and recombinant strains of mice with A/Wy, BALB/c, C3H, and B10 backgrounds were subjected to treatment with urethane [16].

Biological context of Gzmc

• A cDNA clone corresponding to the complete amino acid sequence of a putative protease CCP2 of murine cytotoxic T lymphocytes was isolated and sequenced [17].
• These results suggest that granzyme C rapidly induces target cell death by attacking nuclear and mitochondrial targets and that these targets are distinct from those used by granzyme B to cause classical apoptosis [18].
• Cell death induced by granzyme C [18].
• However, granzyme C did cause rapid mitochondrial swelling and depolarization in intact cells or in isolated mitochondria, and this mitochondrial damage was not prevented by cyclosporin A pretreatment [18].
• Graft survival was prolonged significantly compared with livers from normal or syngeneically reconstituted B10 donors [19].

Anatomical context of Gzmc

• cDNA cloning of granzyme C, a granule-associated serine protease of cytolytic T lymphocytes [17].
• The deduced N-terminal amino acid sequence is identical over 40 residues to that of granzyme C, a protease of unknown function present in granules of cytotoxic lymphocytes [17].
• Using antisera against perforin and against granzyme C, one can detect positive cytoplasmic granules in a small fraction of cells on Day 3; by Day 5, 80-90% of the cells are stained [20].
• Within 1 wk of liquid culture in granulocyte/macrophage colony-stimulating factor (GM-CSF), normal B10 BR (H-2k I-E+) mouse liver nonparenchymal cells (NPC) formed loosely adherent myeloid cell clusters that have been shown to contain dendritic cell (DC) progenitors in similar studies of mouse blood or bone marrow [10].
• These cell lines should facilitate future studies of the immunopathogenesis of NSDC in the B10 [1].

Associations of Gzmc with chemical compounds

• Dexamethasone induces the synthesis of a phospholipase A2-inhibitory protein (PLIP) of molecular weight approximately equal to 55,000 from calf thymus and PLIPs of molecular weights 55,000, 40,000, 28,000, and 15,000 from A/J mouse thymus and from 12-day embryonic B10 [21].
• The S-DIC subline, when exposed for 8 to 12 transplant generations to dimethyltriazenoimidazolecarboxamide, became immunogenic for syngeneic B10 mice, as judged from prolongation of survival time [22].
• B10 (H-2b) mice conditioned with ALG on day -3, 300 cGy of TBI with transplantation of B10.BR (H-2k) or BALB/c (H-2d) BM on day 0, and CyP on day +2 exhibited evidence of donor chimerism (49.6 +/- 3.7% and 38.2 +/- 2.4%, respectively) in 97% of recipients [23].
• Low-dose streptozotocin treatment was performed in mice of H-2 congenic strains on B10, C3H, or A background [12].
• We have studied the idiotype and fine specificity of the secondary immune response to phosphocholine (PC) in C57BL (B10, B10.D2, and B.C8) and BALB (BALB/c, BAB-14, and C.B20) congenic strains of mice [24].

Enzymatic interactions of Gzmc

• Granzyme C branched off first after the primate-rodent split and was involved in a recombination event with granzyme B before the rat-mouse divergence [25].

Regulatory relationships of Gzmc

• However, CCP-2 cells failed to express calcitonin receptors, a mature osteoclast marker, even after coculture with osteoblast ST2 cells in the presence of 1alpha, 25-dihydroxyvitamin D3 [1alpha, 25-(OH)2D3] [26].

Other interactions of Gzmc

• These characteristics are also shared with the CCP1 and CCP2 genes, the charter members of the CCP gene family [27].
• The association of Vbeta family bias and IL-4 inducibility in thymus CD161-CD44lowCD4+CD8- T cells is found for B6, B10, BALB/c, CBA, B10.A(4R), and ICR mouse strains [28].
• An (SJL/J x B10. S)F1 x B10.S backcross was analyzed, and one quantitative trait locus (QTL) was located in the telomeric region of chromosome 10 close to the Ifng locus [29].
• BM from B10 (H2b) mice given FL (10 microg/day; days 0-8; FL-BM) contained a 7-fold higher incidence of potentially tolerogenic immature CD11c+ DC (CD40low, CD80low, CD86low, MHC IIlow) that induced alloantigen-specific T cell hyporesponsiveness in vitro [30].
• Consistent with this, expressions of the inducible isoform of NO synthase (iNOS) protein and mRNA were significantly higher in the spleen of B10 mice than in that of BALB/c mice [3].

Analytical, diagnostic and therapeutic context of Gzmc

• Survival of B10 cardiac allografts in C3H mice given B10 TGF-beta-transduced DC (2x106 IV, 7 days before transplantation), was extended modestly but significantly [31].
• In this study, the role of liver nonparenchymal cells (NPC) in second-set rejection was tested by donor whole-body irradiation and replacement of donor B10 liver NPC with those of either third-party (BALB/c) or recipient strain (C3H) bone marrow [19].
• Livers are accepted spontaneously when transplanted orthotopically from B10 (H2b) or BALB/c (H2d) to C3H (H2k) mice without host immunosuppression [19].
• Irradiation alone (9.5 Gy) of normal B10 donors before liver transplantation significantly prolonged graft survival in presensitized C3H recipients [19].
• We focused our studies on granzyme C. Northern blots showed very high levels of granzymes B and C mRNA expression in M52.34.1 cells 3 days following T cell activation [32].

References