Absence of CD5 Dramatically Reduces Progression of Pulmonary Inflammatory Lesions in SHP-1 Protein-Tyrosine Phosphatase-Deficient ‘Viable Motheaten’ Mice

Joliat, Melissa J.; Lang, Pamela A.; Lyons, Bonnie L.; Burzenski, Lisa M.; Lynes, Michael A.; Yi, Taolin; Sundberg, John P.; Shultz, Leonard D.

doi:10.1006/jaut.2001.0570

Cited by 9 publications

(4 citation statements)

References 78 publications

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“…In this study, we showed that the Sle2 effect on the size of the perC B-1a compartment is independent of CD5 signaling. This confirms earlier work with other strains of mice (22). Interestingly, in the absence of CD5-negative regulatory signals, the phenotypes of the B6.Sle2 mice was largely unchanged, suggesting that the level of activation seen in Sle2 B cells has reached a plateau that cannot be pushed further.…”

Section: Discussionsupporting

confidence: 88%

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Mechanisms of Peritoneal B-1a Cells Accumulation Induced by Murine Lupus Susceptibility LocusSle2

Xu¹,

Butfiloski

Sobel

et al. 2004

The Journal of Immunology

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The abundance of B-1a cells found in the peritoneal cavity of mice is under genetic control. The lupus-prone mouse New Zealand Black and New Zealand White (NZB × NZW)F1 and its derivative NZM2410 are among the strains with the highest numbers of peritoneal B1-a cells. We have previously identified an NZM2410 genetic locus, Sle2, which is associated with the production of large numbers of B-1a cells. In this paper, we examined the mechanisms responsible for this phenotype by comparing congenic C57BL/6 mice with or without Sle2. Fetal livers generated more B-1a cells in B6.Sle2 mice, providing them with a greater starting number of B-1a cells early in life. Sle2-expressing B1-a cells proliferated significantly more in vivo than their B6 counterparts, and reciprocal adoptive transfers showed that this phenotype is intrinsic to Sle2 peritoneal B cells. The rate of apoptosis detected was significantly lower in B6.Sle2 peritoneal cavity B-1a cells than in B6, with or without exogenous B cell receptor cross-linking. Increased proliferation and decreased apoptosis did not affect Sle2 peritoneal B-2 cells. In addition, a significant number of peritoneal cavity B-1a cells were recovered in lethally irradiated B6.Sle2 mice reconstituted with B6.Igha bone marrow, showing radiation resistance in Sle2 B-1a cells or its precursors. Finally, B6.Sle2 adult bone marrow and spleen were a significant source of peritoneal B-1a cells when transferred into B6.Rag2−/− mice. This suggests that peritoneal B-1a cells are replenished throughout the animal life span in B6.Sle2 mice. These results show that Sle2 regulates the size of the B-1a cell compartment at multiple developmental checkpoints.

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Section: Discussionsupporting

confidence: 88%

“…It has already been reported that CD5 deficiency does not affect B-1 cell development in either normal or motheaten mice (22). However, CD5 expression could alter the strength of BCR signaling in the context of Sle2 expression, and consequently impact the number of B-1a cells generated by B6.Sle2 mice.…”

mentioning

confidence: 91%

Mechanisms of Peritoneal B-1a Cells Accumulation Induced by Murine Lupus Susceptibility LocusSle2

Xu¹,

Butfiloski

Sobel

et al. 2004

The Journal of Immunology

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“…In addition, our laboratory has demonstrated that SHP‐1 is necessary for the normal differentiation and distribution of all glial subtypes within the murine CNS (Wishcamper et al, 2001). Although overwhelming evidence from the hematopoietic system indicates that SHP‐1 is a negative regulator of cell signaling cascades (Mason et al, 1997; Berg et al, 1998; Kozlowski et al, 1998; Christianson et al, 2002; Joliat et al, 2002), its expression and function in the CNS are only now beginning to be elucidated.…”

mentioning

confidence: 99%

Motheaten (me/me) mice deficient in SHP‐1 are less susceptible to focal cerebral ischemia

Beamer

Brooks

Lurie

2006

J of Neuroscience Research

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We have demonstrated previously that the protein tyrosine phosphatase SHP-1 seems to play a role in glial development and is upregulated in non-dividing astrocytes after injury. The present study examines the effect of loss of SHP-1 on the CNS response to permanent focal ischemia. SHP-1 deficient (me/me) mice and wild-type littermates received a permanent middle cerebral artery occlusion (MCAO). At 1, 3, and 7 days after MCAO, infarct volume, neuronal survival and cell death, gliosis, and inflammatory cytokine levels were quantified. SHP-1 deficient me/me mice display smaller infarct volumes at 7 days post-MCAO, increased neuronal survival within the ischemic penumbra, and decreased numbers of cleaved caspase 3+ cells within the ischemic core compared with wild-type mice. In addition, me/me mice exhibit increases in GFAP+ reactive astrocytes, F4-80+ microglia, and a concomitant increase in the level of interleukin 12 (IL-12) over baseline compared with wild-type. Taken together, these results demonstrate that loss of SHP-1 results in greater healing of the infarct due to less apoptosis and more neuronal survival in the ischemic core and suggests that pharmacologic inactivation of SHP-1 may have potential therapeutic value in limiting CNS degeneration after ischemic stroke.

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“…H&E-stained tissue sections of the fixed samples were prepared and evaluated by microscopy as described previously (10). Preparation of frozen tissue sections and immunohistochemistry were performed following established procedures (26). The Abs used for immunohistochemistry were anti-CD4 (rat mAb, clone GK1.5; BD Biosciences), anti-CD8 (rat mAb, clone 53-6.7.5; BD Biosciences), anti-F4/80 (rat mAb, clone A3-1; Serotec), and anti-asialo-GM1 (rabbit polyclonal; Cedarlane Laboratories).…”

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

Sodium Stibogluconate Interacts with IL-2 in Anti-Renca Tumor Action via a T Cell-Dependent Mechanism in Connection with Induction of Tumor-Infiltrating Macrophages

Fan¹,

Zhou²,

Pathak³

et al. 2005

The Journal of Immunology

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IL-2 therapy results in 10–20% response rates in advanced renal cell carcinoma (RCC) via activating immune cells, in which the protein tyrosine phosphatase Src homology 2 domain-containing phosphatase 1 (SHP-1) is a key negative regulator. Based on finding that sodium stibogluconate (SSG) inhibited SHP-1, the anti-RCC potential and action mechanism of SSG and SSG/IL-2 in combination were investigated in a murine renal cancer model (Renca). Despite its failure to inhibit Renca cell proliferation in cultures, SSG induced 61% growth inhibition of Renca tumors in BALB/c mice coincident with an increase (2-fold) in tumor-infiltrating macrophages (Mφ). A combination of SSG and IL-2 was more effective in inhibiting tumor growth (91%) and inducing tumor-infiltrating Mφ (4-fold), whereas IL-2 alone had little effect. Mφ increases were also detected in the spleens of mice treated with SSG (3-fold) or SSG/IL-2 in combination (6-fold), suggesting a systemic Mφ expansion similar to those in SHP-deficient mice. T cell involvement in the anti-Renca tumor action of the combination was suggested by the observations that the treatment induced spleen IFN-γ T cells in BALB/c mice, but failed to inhibit Renca tumor growth in athymic nude mice and that SSG treatment of T cells in vitro increased production of IFN-γ capable of activating tumoricidal Mφ. The SSG and SSG/IL-2 combination treatments were tolerated in the mice. These results together demonstrate an anti-Renca tumor activity of SSG that was enhanced in combination with IL-2 and functions via a T cell-dependent mechanism with increased IFN-γ production and expansion/activation of Mφ. Our findings suggest that SSG might improve anti-RCC efficacy of IL-2 therapy by enhancing antitumor immunity.

show abstract

Absence of CD5 Dramatically Reduces Progression of Pulmonary Inflammatory Lesions in SHP-1 Protein-Tyrosine Phosphatase-Deficient ‘Viable Motheaten’ Mice

Cited by 9 publications

References 78 publications

Mechanisms of Peritoneal B-1a Cells Accumulation Induced by Murine Lupus Susceptibility LocusSle2

Mechanisms of Peritoneal B-1a Cells Accumulation Induced by Murine Lupus Susceptibility LocusSle2

Motheaten (me/me) mice deficient in SHP‐1 are less susceptible to focal cerebral ischemia

Sodium Stibogluconate Interacts with IL-2 in Anti-Renca Tumor Action via a T Cell-Dependent Mechanism in Connection with Induction of Tumor-Infiltrating Macrophages

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