Specific Immunity to Streptozocin: Cellular Requirements for Induction of Lymphoproliferation

Klinkhammer, Christiane; Popowa, Poly; Gleichmann, Helga

doi:10.2337/diab.37.1.74

Cited by 43 publications

(11 citation statements)

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“…Transfer of activated spleen cells from LDSTZ-D mice produced diabetes in recipients after a single low dose of STZ (24). STZ-specific immune reactions could be demonstrated by a popliteal lymph node assay indicating immune reactivity stimulated by STZ as an exogenous agent (25). However, depletion of T-lymphocytes alone, although able to temporarily protect from LDSTZ-D, was not sufficient to prevent the development of hyperglycemia (26).…”

Section: Discussionmentioning

confidence: 97%

Fish Oil–Enriched Diet and Reduction of Low-Dose Streptozocin–Induced Hyperglycemia: Inhibition of Macrophage Activation

et al. 1989

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Repeated low doses of streptozocin (STZ; 40 mg/kg, 5 injections/day) induce hyperglycemia in certain strains of mice after a latency of 1 wk. Omega-3 polyunsaturated fatty acids (omega 3FA) have been reported to suppress immune processes by blockade of the cyclooxygenase pathway of arachidonic acid metabolism. We investigated the effects of diets high in omega 3FA on the development of diabetes in the low-dose STZ-induced diabetes (LDSTZ-D) model. Male C57BL/6J mice were on a fish oil diet (FOD) as a source of omega 3FA 8 wk before STZ injection. Controls received laboratory chow only or a coconut oil diet (COD). Blood glucose levels in FOD mice were reduced (12.5 vs. 28 mM for COD mice, P less than .001) 60 days after STZ injection with a diet in which 20% of the calories were from fish oil. In FOD mice, immunohistology showed reduced numbers of class II antigen-expressing cells in pancreatic islets followed by a decreased extent of insulitis. FOD significantly decreased the number of Fc receptor-negative dendritic cells in cytospin preparations of islets isolated from diabetic mice. Interleukin 1-like activity of peritoneal exudate cell supernatants isolated from mice on FOD was reduced. FOD did not improve insulin secretion of isolated islets from LDSTZ-D mice. These data indicate a beneficial effect of FOD on the immune component of the mouse LDSTZ-D model.

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Section: Discussionmentioning

confidence: 97%

Fish Oil–Enriched Diet and Reduction of Low-Dose Streptozocin–Induced Hyperglycemia: Inhibition of Macrophage Activation

et al. 1989

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“…STZ, a nitrosourea derivative approved for the treatment of carcinoid and pancreatic islet cell tumors, is known to induce type I diabetes in both animals (Like and Rossini 1976;Cheta 1998) and man (Schulz et al 1990). STZ was repeatedly shown to induce markedly positive PLN responses (Klinkhammer et al 1988;Verdier et al 1990;Krzystyniak et al 1992a, b;Brouland et al 1994;Patriarca et al 1994;Vial et al 1997;Aida et al 1998) and is therefore considered a prototypic reference compound in the PLN assay.…”

Section: Discussionmentioning

confidence: 97%

“…STZ was repeatedly shown to cause strongly positive PLN responses in rats and mice (Klinkhammer et al 1988;Verdier et al 1990;Krzystyniak et al 1992a, b;Brouland et al 1994;Patriarca et al 1994;Vial et al 1997;Aida et al 1998). As mentioned above, a pseudoGvH reaction is presumably involved.…”

Section: Introductionmentioning

confidence: 94%

Popliteal lymph node responses to acetone and ethanol differ from those induced by streptozotocin

Choquet-Kastylevsky¹,

Descotes²

2004

Arch Toxicol

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The popliteal lymph node (PLN) assay was proposed to detect the potential of immunotoxicants for inducing systemic autoimmune-like reactions, but also xenobiotics that are sensitizing or exert immunostimulatory properties. Results on over 100 chemicals, mostly pharmaceuticals, are available with the PLN assay and show many correlations between rodent data and the clinical experience. A major issue is that the mechanisms involved have not been fully elucidated. In order to provide mechanistic clues to improve the predictability of the PLN assay, the effects of streptozotocin (STZ) were compared to those of ethanol and acetone in normal C57Bl/6 mice as well as mice depleted in CD4+ or CD8+ T-cells by treatment with specific monoclonal antibodies. STZ, ethanol and acetone gave similar positive responses in normal mice. Neither CD4+ nor CD8+ T-cell depletion influenced the PLN responses to ethanol or acetone, whereas CD8+ in contrast to CD4+ T-cell depletion abolished the response to STZ. There was an increase in the production of IL-6 and IFN-gamma mRNAs measured by RT-PCR in STZ-, but not in ethanol- or acetone-treated normal mice. The production of TNFalpha, IL-1alpha, IL-1beta, IL-2R and IL-12 mRNAs was increased whatever the treatment, but increases were 2- to 3-fold greater after STZ than ethanol or acetone. These results suggest that PLN responses to primary irritants such as ethanol and acetone essentially reflect non-specific inflammation, whereas PLN responses to an autoimmunogenic compound such as STZ involve CD8+ T lymphocytes and the production of IFN-gamma and IL-6. These findings may prove useful to improve the predictability of the PLN assay.

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“…To investigate the tracer accumulation in inflammatory LNs, two different lymphadenitis models, a chronic streptozotocin (STZ)-induced lymphadenitis model [17] and an acute concanavalin A (Con A) lymphadenitis model [18] were established.…”

Section: Methodsmentioning

confidence: 99%

O-(2-[18F]Fluoroethyl)-L-tyrosine (FET): a tracer for differentiation of tumour from inflammation in murine lymph nodes

et al. 2002

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High uptake of [(18)F]fluoro-2-deoxy- D-glucose (FDG) by inflammatory cells is a frequent cause of false positive results in lymph node (LN) staging by positron emission tomography. Previous studies suggest that radiolabelled amino acids may be more specific markers for viable tumour tissue than FDG. The aim of this study was to investigate quantitatively the uptake of FDG, [(3)H]methyl- L-methionine (MET) and O-2-([(18)F]fluoroethyl)- L-tyrosine (FET) in tumour-infiltrated and immunologically stimulated LNs. Popliteal LNs of Balb/c and DBA/2 mice were stimulated by injection into the right posterior foot pad of mice of either streptozotocin (STZ), causing chronic lymphadenitis, or concanavalin A (Con A), resulting in acute lymphadenitis. Tumour-infiltrated popliteal LNs were induced by inoculation of 2x10(5) lacZ-tagged T cell mouse lymphoma cells into the right posterior foot pad of syngeneic mice. Twenty-one days post inoculation of tumour cells or at various time points after STZ or Con A injection, mice were simultaneously injected intravenously with MET and FDG or MET and FET. After 30 min, mice were sacrificed and tracer uptake was determined in popliteal LNs. Contralateral LNs and LNs of untreated mice served as controls. Histopathological and immunohistochemical analysis demonstrated typical signs of chronic inflammation (non-specific sinus hyperplasia with macrophages) in STZ-treated animals and acute inflammatory changes (accumulation of neutrophilic granulocytes, vascular dilation, follicular hyperplasia) in Con A-treated animals. X-Gal staining confirmed the presence of tumour cells in the LNs of the injected side of tumour-inoculated mice. In the chronic lymphadenitis model, FDG uptake increased 3.0+/-0.1 fold [from 2.7+/-0.2 to 8.2+/-1.2 percent of injected dose per gram tissue (%ID/g)] and MET uptake 2.0+/-0.01 fold (from 4.5+/-0.6 to 9.2+/-1.1 %ID/g). In the acute lymphadenitis model, FDG uptake increased 3.9+/-0.3 fold (from 2.7+/-0.2 to 10.6+/-2.4 %ID/g) and MET uptake 1.9+/-0.1 fold (from 4.5+/-0.6 to 8.5+/-1.4 %ID/g). In contrast, FET uptake in both lymphadenitis models (1.0+/-0.03 and 1.2+/-0.04 fold) was not significantly different from that in controls (from 4.2+/-0.3 to 4.7+/-0.7 and to 5.1+/-0.4 %ID/g, respectively). Uptake of all three tracers in tumour-infiltrated LNs was significantly higher than that in control LNs. FDG uptake increased 2.8+/-0.15 fold (from 2.7+/-0.2 to 7.6+/-1.3%ID/g), MET uptake 1.7+/-0.11 fold (from 4.5+/-0.6 to 7.5+/-1.3 %ID/g) and FET uptake 2.4+/-0.15 fold (from 4.2+/-0.3 to 10.0+/-1.8 %ID/g). MET and FDG uptake was similar or higher in inflammatory than in tumour-infiltrated LNs ( P=0.01 and P<0.01, respectively). In contrast, uptake of FET showed no overlap between tumour-infiltrated and inflammatory LNs ( P<0.00001). In conclusion, tumour-infiltrated and inflammatory LNs could not be differentiated by means of FDG and MET uptake. FET, in contrast, proved to be a specific tracer for differentiating between tumour-infiltrated and inflammatory LNs in the murin...

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Specific Immunity to Streptozocin: Cellular Requirements for Induction of Lymphoproliferation

Cited by 43 publications

References 0 publications

Fish Oil–Enriched Diet and Reduction of Low-Dose Streptozocin–Induced Hyperglycemia: Inhibition of Macrophage Activation

Fish Oil–Enriched Diet and Reduction of Low-Dose Streptozocin–Induced Hyperglycemia: Inhibition of Macrophage Activation

Popliteal lymph node responses to acetone and ethanol differ from those induced by streptozotocin

O-(2-[18F]Fluoroethyl)-L-tyrosine (FET): a tracer for differentiation of tumour from inflammation in murine lymph nodes

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