Mouse strain differences in resident peritoneal cells: a flow cytometric analysis

Festing, Michael F. W.; Legg, R.F.; Eydmann, Trevor; Brammall, A.

doi:10.1258/002367790780890374

Cited by 10 publications

(7 citation statements)

References 13 publications

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“…In contrast, an analysis of total cells in a peritoneal lavage revealed that Balb/c mice contained a large population of small cells (low FSc) with minimal intracellular complexity (low SSc), whereas this population of cells was minimal in C57BL/6 mice (Additional file 1 : Figure S1). These observations confirm the results of Festing et al [ 76 ] that peritoneal cells in Balb/c mice expressed a high ‘lymphocyte’ to ‘macrophage’ ratio whereas the reverse occurs in C57BL strains. Within 24 h after injection of peptide, the population of small cells largely disappeared in Balb/c mice but increased in C57BL/6 mice (Additional file 1 : Figure S1).…”

Section: Resultssupporting

confidence: 92%

An innovative immunotherapeutic strategy for ovarian cancer: CLEC10A and glycomimetic peptides

Eggink¹,

Roby²,

Cote³

et al. 2018

j. immunotherapy cancer

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BackgroundReceptors specific for the sugar N-acetylgalactosamine (GalNAc) include the human type II, C-type lectin receptor macrophage galactose-type lectin/C-type lectin receptor family member 10A (MGL/CLEC10A/CD301) that is expressed prominently by human peripheral immature dendritic cells, dendritic cells in the skin, alternatively-activated (M2a) macrophages, and to lesser extents by several other types of tissues. CLEC10A is an endocytic receptor on antigen-presenting cells and has been proposed to play an important role in maturation of dendritic cells and initiation of an immune response. In this study, we asked whether a peptide that binds in the GalNAc-binding site of CLEC10A would serve as an effective tool to activate an immune response against ovarian cancer.MethodsA 12-mer sequence emerged from a screen of a phage display library with a GalNAc-specific lectin. The peptide, designated svL4, and a shorter peptide consisting of the C-terminal 6 amino acids, designated sv6D, were synthesized as tetravalent structures based on a tri-lysine core. In silico and in vitro binding assays were developed to evaluate binding of the peptides to GalNAc-specific receptors. Endotoxin-negative peptide solutions were administered by subcutaneous injection and biological activity of the peptides was determined by secretion of cytokines and the response of peritoneal immune cells in mice. Anti-cancer activity was studied in a murine model of ovarian cancer.ResultsThe peptides bound to recombinant human CLEC10A with high avidity, with half-maximal binding in the low nanomolar range. Binding to the receptor was Ca2+-dependent. Subcutaneous injection of low doses of peptides into mice on alternate days resulted in several-fold expansion of populations of mature immune cells within the peritoneal cavity. Peptide sv6D effectively suppressed development of ascites in a murine ovarian cancer model as a monotherapy and in combination with the chemotherapeutic drug paclitaxel or the immunotherapeutic antibody against the receptor PD-1. Toxicity, including antigenicity and release of cytotoxic levels of cytokines, was not observed.Conclusionsv6D is a functional ligand for CLEC10A and induces maturation of immune cells in the peritoneal cavity. The peptide caused a highly significant extension of survival of mice with implanted ovarian cancer cells with a favorable toxicity and non-antigenic profile.Electronic supplementary materialThe online version of this article (10.1186/s40425-018-0339-5) contains supplementary material, which is available to authorized users.

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Section: Resultssupporting

confidence: 92%

An innovative immunotherapeutic strategy for ovarian cancer: CLEC10A and glycomimetic peptides

Eggink¹,

Roby²,

Cote³

et al. 2018

j. immunotherapy cancer

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“…However, the peritoneum differs from organized lymphoid tissue by having greater numbers of B-1 B cells, fewer T cells, and more macrophages (Hardy 2006; Turchyn et al 2007), factors likely to impact T cell biology both in vivo and in vitro . The strain differences in PerC T cell biology described in this report parallel differences in B-1 B cell and macrophage composition reported among mouse strains (Stadler and de Week 1980; Hayakawa et al 1984; Festing et al 1990; Turchyn et al 2007). The reduced number of B-1B cells and increased macrophage representation in XID mice likely combine to contribute to their distinctive PerC T cell biology.…”

Section: Discussionsupporting

confidence: 77%

Peritoneal T lymphocyte regulation by macrophages

et al. 2011

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The T cell composition of the peritoneal cavity (PerC) in naïve BALB/c, C57BL/6, DBA/2J, and B-1 B cell-defective BALB.xid mice was investigated. The BALB.xid PerC T cell pool had a high CD4:CD8 T cell ratio relative to the other strains whose ratios were similar to those found in their lymph node and spleen. All mice had significant representation of T cells with an activated (CD25 + , GITR hi , CD44 hi , CD45RB lo , CD62L lo ) phenotype and low numbers of Foxp3 + T reg cells in their PerC. Despite a phenotype indicative of activation, peritoneal T cell responses to CD3 ligation were very low for C57BL/6 and BALB.xid, but not BALB/c, mice. Enzyme inhibition and cytokine neutralization studies revealed active suppression of the T cell response mediated by the macrophages that represent a significant portion of PerC leucocytes. Driven by IFNγ to express iNOS, macrophages suppressed T cell activation in vitro by arginine catabolism. Although BALB/ c T cells were also in a macrophage-dense environment their limited IFNγ production failed to trigger suppression. This difference between BALB/c and BALB.xid PerC T cells suggests a role for xid in shaping macrophage-mediated immune regulation.

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“…3D). Lastly, we tested the phagocytic capacity of macrophages by scoring latex bead uptake (28), which was again increased in Mclk1 +/2 cells (Fig. 3E).…”

Section: Increased Classic Activation Of Macrophagesmentioning

confidence: 99%

Elevated Mitochondrial Reactive Oxygen Species Generation Affects the Immune Response via Hypoxia-Inducible Factor-1α in Long-Lived Mclk1+/− Mouse Mutants

Wang¹,

Malo

Hekimi³

2009

The Journal of Immunology

117

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Mitochondrial reactive oxygen species (ROS) are believed to stabilize hypoxia-inducible factor (HIF)-1α, a transcriptional regulator of the immune response. Mclk1 encodes a mitochondrial protein that is necessary for ubiquinone biosynthesis. Heterozygote Mclk1+/− mutant mice are long-lived despite increased mitochondrial ROS and decreased energy metabolism. In this study, Mclk1+/− mutant mice in the C57BL/6J background displayed increased basal and induced expression of HIF-1α in liver and macrophages in association with elevated expression of inflammatory cytokines, in particular TNF-α. Mutant macrophages showed increased classical and decreased alternative activation, and mutant mice were hypersensitive to LPS. Consistent with these observations in vivo, knock-down of Mclk1 in murine RAW264.7 macrophage-like cells induced increased mitochondrial ROS as well as elevated expression of HIF-1α and secretion of TNF-α. We used an antioxidant peptide targeted to mitochondria to show that altered ROS metabolism is necessary for the enhanced expression of HIF-1α, which, in turn, is necessary for increased TNF-α secretion. These findings provide in vivo evidence for the action of mitochondrial ROS on HIF-1α activity and demonstrate that changes in mitochondrial function within physiologically tolerable limits modulate the immune response. Our results further suggest that altered immune function through a limited increase in HIF-1α expression can positively impact animal longevity.

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Mouse strain differences in resident peritoneal cells: a flow cytometric analysis

Cited by 10 publications

References 13 publications

An innovative immunotherapeutic strategy for ovarian cancer: CLEC10A and glycomimetic peptides

An innovative immunotherapeutic strategy for ovarian cancer: CLEC10A and glycomimetic peptides

Peritoneal T lymphocyte regulation by macrophages

Elevated Mitochondrial Reactive Oxygen Species Generation Affects the Immune Response via Hypoxia-Inducible Factor-1α in Long-Lived Mclk1+/− Mouse Mutants

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