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Results for “BALB/c mouse model”

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PubMed1995

Induction of proteinuria by adriamycin or bovine serum albumin in the mouse.

To establish models of proteinuria in the mouse, BALB/c mice were injected with puromycin aminonucleoside (PAN, 1.5 or 4.5 mg/10 g body weight), adriamycin (AD, 0.2 mg/10 g body weight) intravenously or bovine serum albumin (BSA, 100 mg/10 g body weight) intraperitoneally. Proteinuria was measured as the ratio of urinary albumin (micrograms/ml) to creatinine (mg/dl) and further characterized by isotyping the immunoglobulin. Although not obtained with PAN (followed for 4 weeks), proteinuria was readily attained in the mouse after treatment with AD or BSA. Most AD-treated mice (5/7) developed an abrupt increase of proteinuria at day 2 after injection, with the ratio of urinary albumin to creatinine in the range 0.28-0.45. The degree of proteinuria increased with time and all mice tested (7/7) showed overt proteinuria at day 4. These mice became anuric at day 5 and died at days 6 and 7. For BSA, 4 h after administration, four of seven mice showed enhanced proteinuria, lasting 8 h with urinary albumin and creatinine in a ratio < 0.05. Isotyping of urine samples collected at the time of heavy proteinuria (ratio of urinary albumin to creatinine: > 0.40 for AD-treated mice, > 0.15 for BSA-treated mice) showed that all of the mice (7/7) with AD-induced proteinuria (ADp) and three of four mice with BSA-induced proteinuria (BSAp) revealed urinary IgG2b and IgA, while only one of seven control mice showed IgG2b alone in urine. The mice were sacrificed at the time they presented with heavy proteinura for pathologic and anionic studies on renal tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1997

Respiratory syncytial virus triggers synthesis of IL-6 in BALB/c mouse alveolar macrophages in the absence of virus replication.

Cytokines produced by alveolar macrophages are likely involved in the regulation of the immune response arising from respiratory syncytial virus (RSV) infection. Both infectious and UV-inactivated RSV were effective in inducing BALB/c mouse alveolar macrophages to synthesize increased levels of IL-6 mRNA and secreted IL-6 protein. No increase in IL-1beta (either mRNA or secreted protein) was observed. The augmented production of IL-6 was activated by purified virus and was reduced by pretreating virus with virus-neutralizing antiserum, demonstrating a requirement for virus in the enhanced IL-6 response. The results suggest that the exposure of BALB/c alveolar macrophages to small quantities of RSV (in the absence of detectable virus replication) is sufficient to trigger IL-6 production. The finding that UV-inactivated virus was effective in triggering IL-6 production by mouse alveolar macrophages is similar to that reported in human alveolar macrophages, providing further validation of the BALB/c mouse as a useful animal model for human RSV infection.

Animals↗

PubMed2004

Essential role of dendritic cell CD80/CD86 costimulation in the induction, but not reactivation, of TH2 effector responses in a mouse model of asthma.

BACKGROUND: Airway dendritic cells (DCs) are crucial for the generation of TH2 cells from naive T cells during sensitization and for reactivation of primed TH2 cells on allergen challenge in mouse models of asthma. It is unknown whether CD80/CD86 costimulation is necessary during both phases of the response because primed T cells rely less on costimulatory molecules compared with naive T cells. OBJECTIVE: We sought to study the contribution of CD80/CD86 costimulatory molecules on DCs during sensitization or challenge in a mouse model of asthma. METHODS: Naive BALB/c mice received an intratracheal injection of ovalbumin (OVA)-pulsed DCs obtained from the bone marrow of wild-type (WT) or CD80/CD86-/- mice and were subsequently challenged with OVA aerosol to address the role of costimulation during sensitization. OVA-sensitized mice received OVA-pulsed WT or CD80/CD86-/- DCs without OVA aerosol to address the role of costimulation during challenge. RESULTS: WT DCs induced the proliferation and effector TH2 differentiation of naive OVA-specific T cells, whereas CD80/CD86-/- DCs induced only proliferation. Not surprisingly, WT DCs but not CD80/CD86-/- DCs induced sensitization to OVA in naive mice. In contrast, in OVA-sensitized mice intratracheal injection of CD80/CD86-/- OVA-pulsed DCs led to eosinophilic airway inflammation, goblet cell hyperplasia, and effector TH2 cytokine production that was not different from that seen after injection with WT OVA-DCs, even when the inducible costimulator ICOS was blocked or cytotoxic T lymphocyte-associated antigen 4 immunoglobulin was given. CONCLUSION: CD80/CD86 costimulation on DCs is only necessary during priming of naive T cells into TH2 cells but not during restimulation of previously primed TH2 cells in the challenge phase.

Animals↗

PubMed2006

Serine protease inhibitors nafamostat mesilate and gabexate mesilate attenuate allergen-induced airway inflammation and eosinophilia in a murine model of asthma.

BACKGROUND: Serine proteases such as mast cell tryptase and certain allergens are important in the pathogenesis of allergic inflammation of asthma. OBJECTIVE: We sought to investigate the effects of serine protease inhibitors nafamostat mesilate (FUT), gabexate mesilate (FOY), and ulinastatin (UTI) on airway inflammation in a mouse model of allergic asthma. METHODS: BALB/c mice were sensitized to Dermatophagoides pteronyssinus (Der p) and intratracheally challenged with Der p (0.5 mg/mL). Therapeutic doses of FUT (0.0625 mg/kg), FOY (20 mg/kg), and UTI (10,000 U/kg) were intra-peritoneally injected into 3 corresponding sensitized mice during the sensitization phase (protocol 1) or 24 hours after allergen challenge (protocol 2). RESULTS: Both FUT-treated and FOY-treated sensitized mice had reduced mast cells activation, airway hyperresponsiveness, attenuated eosinophils infiltrations, and decreased Der p-induced IL-4 and TNF-alpha, but increased IL-12 cytokine production in bronchoalveolar lavage fluid compared with nontreated mice. Furthermore, FUT treatment downregulated the expression of IL-1beta, TNF-alpha, IL-6, eotaxin, inducible NO synthase, CD86, and nuclear factor-kappaB activation, but enhanced the expression of IL-12 and IL-10 in Der p-stimulated alveolar macrophages. UTI-treated mice have no significant change of the aforementioned measurements compared with nontreated sensitized mice. CONCLUSION: Nafamostat mesilate and FOY exerting the therapeutic effect in allergen-induced airway inflammation was a result not only of their inhibitory action in the early phase of mast cells activation but also of immunoregulatory function in the late phase of allergic inflammation. Such properties of FUT and FOY might be a potential therapeutic approach for asthma. CLINICAL IMPLICATIONS: The clinical used of serine protease inhibitors FUT and FOY may also have implications for treating airway inflammation of asthma.

Animals↗

PubMed1999

Bone marrow stromal cells as a vehicle for gene transfer.

Adoptive transfer of genetically modified somatic cells is playing an increasingly important role in the management of a wide spectrum of human diseases. Hematopoietic stem cells and lymphocytes have been used to transfer a variety of genes, however, they have limitations. In this study, the feasibility of retroviral gene transduction of bone marrow stromal cells, and the engraftment characteristics of these cells following infusion, was investigated in a murine transplantation model. Stromal cells derived from Balb/c mouse bone marrow were transduced with a replication-defective retrovirus containing the LacZ gene. Following three rounds of transduction, between 5 and 40% of the cells were positive for the LacZ gene. A total of 2 x 106 cells were infused into the same mouse strain. After the infusion, the LacZ gene was detected by PCR in the bone marrow, spleen, liver, kidney and lung; however, only the spleen and bone marrow samples were strongly positive. Quantitative PCR demonstrated that between 3 and 5% of spleen and bone marrow cells, and 1% of liver cells contained the LacZ gene at 3 weeks after infusion; <0.2% transduced cells were found in other organs. No difference was noted in engraftment between mice with or without irradiation before transplantation, suggesting that engraftment occurred without myeloablation. The infused transduced cells persisted for up to 24 weeks. Self-renewal of transplanted stromal cells was demonstrated in secondary transplant studies. Ease of culture and gene transduction and tissue specificity to hematopoietic organs (bone marrow, spleen, liver) is demonstrated, indicating that stromal cells may be an ideal vehicle for gene transfer.

Adoptive Transfer↗

PubMed2003

Progesterone increases airway eosinophilia and hyper-responsiveness in a murine model of allergic asthma.

BACKGROUND: Sex hormones might affect the severity and evolution of bronchial asthma. From existing literature, there exists, however, no convincing evidence for either exacerbation or improvement of allergic symptoms by progesterone. OBJECTIVE: This study was aimed to explore the effect of exogenously administered progesterone in a mouse model of allergic asthma. METHODS: BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injections with OVA followed by chronic inhalation of nebulized OVA or physiologic saline (Sal). Medroxyprogesterone acetate or placebo was instilled daily into the oesophagus before and during the inhalatory OVA challenge phase. RESULTS: Progesterone worsened allergic airway inflammation in OVA-challenged mice, as evidenced by enhanced bronchial responsiveness to inhaled metacholine and increased bronchial eosinophilia. Elevated airway eosinophilia corresponded with higher bronchial and systemic IL-5 levels in the progesterone group. The ratio of IL-4/IFN-gamma levels in bronchoalveolar lavage fluid and numbers of eosinophil colony-forming units in the bone marrow were also elevated in the latter group. Progesterone, however, did not influence allergen-specific IgE production, nor did it affect bronchial responses in Sal-challenged mice. CONCLUSION: Our data show that exogenously administered progesterone aggravates the phenotype of eosinophilic airway inflammation in mice by enhancing systemic IL-5 production. Progesterone also increases bronchial hyper-reactivity.

Animals↗

PubMed2001

Kinetics of leukocyte and myeloid cell traffic in the murine corneal allograft response.

BACKGROUND: Little information exists on the trafficking of myeloid and lymphoid cells between the transplanted cornea and the secondary lymphoid tissue. This study reports on changes in the cornea and the draining lymph node (DLN) from the time of graft emplacement. METHODS: Using a mouse corneal graft model (C57BL/10Sn to BALB/c), eyes and submandibular DLN were examined by immunohistochemistry and three-color flow cytometry for evidence of T cell activation and dendritic cell (DC) conditioning (up-regulation of costimulatory molecules) at various times (15 min to 24 days; n=4 for each time). RESULTS: In the DLN, early (2 hr) DC conditioning was sustained throughout allograft rejection whereas a remarkable drop in percentage of activated CD4+ and CD8+ T cells (P <0.001) was followed by a biphasic rise in activated CD4+ and, to a lesser extent, CD8+ T cells (24 hr, P <0.001 and 6 days, P <0.01). CD11b+ and MOMA-2+ macrophages, MHC Class II+ cells, CD86+ DC, and neutrophils were the earliest cells infiltrating the cornea (at 24 hr), whereas T cells appeared after 2 days, with CD4+ T cells being confined largely to the graft recipient border. CONCLUSIONS: Immediate and rapid changes in T cell and DC populations in the DLN correlate with the type of cellular infiltration in the corneal graft. The data are consistent with a model in which CD4+ T cell help for CD8+ cytotoxic T cells could be provided by sequential two-way activation of T cells and DC in the DLN. The majority of cells infiltrating the graft were macrophages and neutrophils, with fewer DC and T cells.

Animals↗

PubMed2004

Reversibility of airway inflammation and remodelling following cessation of antigenic challenge in a model of chronic asthma.

BACKGROUND: Asthma is associated with recruitment of eosinophils, accumulation of chronic inflammatory cells in the airway walls, subepithelial fibrosis and other structural changes of airway wall remodelling. The role of ongoing exposure to allergens in their pathogenesis remains unclear. OBJECTIVE: To examine whether changes of inflammation and remodelling were reversible following cessation of antigenic challenge in a mouse model of chronic asthma. METHODS: BALB/c mice sensitized to ovalbumin (OVA) were chronically challenged by inhalation of a low mass concentration of antigen for 8 weeks, leading to development of acute-on-chronic airway inflammation, subepithelial fibrosis and other changes of airway wall remodelling. Epithelial injury was assessed by immunohistochemistry, while inflammation and remodelling were quantified by appropriate histomorphometric techniques. Regression of lesions was assessed in animals examined at 1, 2 and 4 weeks after exposure to OVA ceased. RESULTS: We did not find evidence of airway epithelial injury in this model of low-level chronic inhalational exposure to antigen. Persistence of the recruitment of eosinophils and chronic inflammatory cells in the airway walls was dependent on continuing antigenic challenge, as was persistence of mucous cell hyperplasia/metaplasia. Subepithelial fibrosis and epithelial hypertrophy exhibited delayed reversibility following cessation of exposure to antigen, possibly related to matrix-associated accumulation of transforming growth factor-beta(1). CONCLUSION: In chronic asthma, low-level antigenic challenge may be required to maintain the inflammatory response in the airway wall, but airway remodelling may persist in its absence.

Administration, Inhalation↗

PubMed1980

Sequential activation in V genes during postnatal life.

The BALB/c mouse strain represents an excellent model for studying the activation of V genes, because several myeloma proteins share the cross-reactive idiotype with antipolysaccharide antibodies of the same antigenic specificity. In addition, the majority of these antipolysaccharide antibody responses are independent of T help and, therefore, the maturation of helper T cells does not play a role in the study of these responses. Our results, as well as those obtained by other investigators, have shown that immunization of 1-day-old mice elicits an anti-beta 2 leads to 6 fructosan, 384Id anti-S tranaroa LPS, and X24IdX and X24IdI antigalactan response. T15Id+ phosphocholine, IdX+ anti-Ars, and 460Id+ anti-TNP (in response to immunization with TNP-LPS and TNP-Levan) antibody responses can be induced only in 6-to 8-day-old mice. One can obtain 2.4 SSSIII Id+ of anti-SSSIII and 347Id+ antiflagellin antibody responses only in 2-week-old mice. In 4-week-old mice IdX+ anti-beta 2 leads to 1 fructosan was elicited, and QPC52IdX+ anti-alpha 1-6 dextran in 3-month-old mice. These observations suggest a sequential activation of V genes during postnatal life. The theoretical and practical implications of these observations are discussed.

Age Factors↗

PubMed2005

Evaluation of LBM415 (NVP PDF-713), a novel peptide deformylase inhibitor, for treatment of experimental Mycoplasma pneumoniae pneumonia.

Mycoplasma pneumoniae is a major cause of community-acquired pneumonia. We evaluated the efficacy of LBM415, a novel peptide deformylase inhibitor antimicrobial agent, for the treatment of M. pneumoniae pneumonia in a mouse model. Eight-week-old BALB/c mice were intranasally inoculated once with 10(7) CFU of M. pneumoniae. Groups of mice were treated with LBM415 (50 mg/kg of body weight) or placebo subcutaneously daily for 13 days, starting 24 h after inoculation. Groups of mice were evaluated at the baseline; at days of treatment 1, 3, 6, and 13; and at 7 days after treatment. The MIC of LBM415 against M. pneumoniae was <0.005 microg/ml. LBM415-treated mice had significantly lower bronchoalveolar lavage fluid M. pneumoniae concentrations than placebo-treated mice on days 6 and 13 of treatment. Compared with placebo treatment, therapy with LBM415 significantly decreased lung histopathology scores at days 3, 6, and 13 of treatment and at 7 days after treatment. Airway obstruction was significantly lower in LBM415-treated mice than in placebo-treated mice on days 1, 3, and 6 of treatment and after 7 days of therapy, while airway hyperresponsiveness was significantly lower only on day 3 of therapy. The bronchoalveolar lavage fluid concentrations of tumor necrosis factor alpha, gamma interferon (IFN-gamma), interleukin-6 (IL-6), IL-12, KC (functional IL-8), monocyte chemotactic protein 1, macrophage inflammatory protein 1alpha, monokine induced by IFN-gamma, and IFN-inducible protein 10 were significantly reduced in LBM415-treated mice compared with the levels in placebo-treated mice. There were no differences in the bronchoalveolar lavage fluid concentrations of granulocyte-macrophage colony-stimulating factor, IL-1beta, IL-2, IL-4, IL-5, and IL-10 between the two groups of mice. LBM415 therapy had beneficial microbiologic, histologic, respiratory, and immunologic effects on acute murine M. pneumoniae pneumonia.

Airway Obstruction↗

PubMed1986

Comparison of living and nonliving vaccines for Brucella abortus in BALB/c mice.

The BALB/c mouse was selected as a model for infection with Brucella abortus on the basis of protracted nonclinical infection produced by strain 2308, virulent for cattle, and relatively rapid clearance of strain 19, an attenuated strain used to vaccinate cattle. Protection in mice vaccinated with strain 19 was compared with that obtained with nonliving vaccines at early (1 week) and later (4 weeks) intervals after challenge with strain 2308 and assessed by enumeration of B. abortus organisms in the spleen. Mice challenged 4 weeks after vaccination with strain 19 exhibited significant protection at 1 and 4 weeks postinfection (p.i.), with an increased magnitude of protection at the later time. When challenged 6 weeks after vaccination with strain 19, the level of protection diminished between 1 and 4 weeks p.i. and at the later time was not always significantly different from controls. Mice immunized 4 weeks earlier with nonliving vaccines in mineral oil with t trehalose dimycolate (TDM) and muramyl dipeptide (MDP) demonstrated patterns of protection similar to those obtained following the 6 week vaccination-challenge interval with strain 19. Vaccination with cell envelopes derived from strain 2308 produced equivalent protection at 1 week p.i. whether administered in phosphate-buffered saline, incomplete Freund adjuvant, or the TDM and MDP adjuvant. Equivalent protection also followed vaccination with strain 2308 killed whole cells, cell envelopes, or outer membrane proteins in phosphate-buffered saline or in the TDM and MDP adjuvant. The TDM and MDP adjuvant alone induced nonspecific resistance, which peaked at 1 day p.i. and was still present at 1 week p.i., although by this time its magnitude was significantly less than the protection induced by antigen combined with the adjuvant. These data, together with the results of antibody assays and passive and adoptive transfer studies, suggested that protection at 1 week p.i. could be accounted for largely by an effect of O antibodies, with T cell-mediated immune responses having a subsidiary role.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed2001

Intranasal treatment with a recombinant hypoallergenic derivative of the major birch pollen allergen Bet v 1 prevents allergic sensitization and airway inflammation in mice.

BACKGROUND: The major birch pollen allergen Bet v 1 represents one of the most prevalent environmental allergens responsible for allergic airway inflammation. OBJECTIVE: In the present study we sought to compare the complete recombinant Bet v 1 allergen molecule with genetically produced hypoallergenic fragments of Bet v 1 regarding mucosal tolerance induction in a mouse model of allergic asthma. METHODS: BALB/c mice were intranasally treated with recombinant Bet v 1 or with two recombinant Bet v 1 fragments (F I: aa 1-74; F II: aa 75-160) prior to aerosol sensitization with birch pollen and Bet v 1. RESULTS: Intranasal application of F II, containing the major T cell epitope, led to significant reduction of IgE/IgG1 antibody responses, in vitro cytokine production (IL-5, IFN-gamma, IL-10) and negative immediate cutaneous hypersensitivity reactions comparable to the pretreatment with the complete rBet v 1 allergen. Moreover, airway inflammation (eosinophilia, IL-5) was inhibited by the pretreatment with either the complete Bet v 1 or F II. However, for prevention of airway hyperresponsiveness the complete molecule was required. The mechanisms leading to immunosuppression seemed to differ in their dependence on the conformation of the molecules, since tolerance induced with the complete Bet v 1, but not with F II, was transferable with spleen cells and associated with increased TGF-beta mRNA levels. CONCLUSION: We conclude that mucosal tolerance induction with recombinant allergens and genetically engineered hypoallergenic derivatives thereof could provide a convenient and safe intervention strategy against type I allergy.

Administration, Intranasal↗

PubMed2006

Effects of overexpression of IL-10, IL-12, TGF-beta and IL-4 on allergen induced change in bronchial responsiveness.

BACKGROUND: An increasing prevalence of allergic diseases, such as atopic dermatitis, allergic rhinitis and bronchial asthma, has been noted worldwide. Allergic asthma strongly correlates with airway inflammation caused by the unregulated production of cytokines secreted by allergen-specific type-2 T helper (Th2) cells. This study aims to explore the therapeutic effect of the airway gene transfer of IL-12, IL-10 and TGF-beta on airway inflammation in a mouse model of allergic asthma. METHODS: BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injections with OVA and challenged by nebulized OVA. Different cytokine gene plasmids or non-coding vector plasmids were instilled daily into the trachea up to one day before the inhalatory OVA challenge phase. RESULTS: Intratracheal administration of IL-10, IL-12 or TGF-beta can efficiently inhibit antigen-induced airway hyper-responsiveness and is able to largely significantly lower the number of eosinophils and neutrophils in bronchoalveolar lavage fluid of ovalbumin (OVA) sensitized and challenged mice during the effector phase. Furthermore, the effect of IL-10 plasmids is more remarkable than any other cytokine gene plasmid. On the other hand, local administration of IL-4 gene plasmids before antigen challenge can induce severe airway hyper-responsiveness (AHR) and airway eosinophilia. CONCLUSION: Our data demonstrated that anti-inflammatory cytokines, particularly IL-10, have the therapeutic potential for the alleviation of airway inflammation in murine model of asthma.

Animals↗

PubMed2006

A novel mouse model for preeclampsia by transferring activated th1 cells into normal pregnant mice.

Immunological imbalances have been hypothesized as a cause for the onset of preeclampsia, which is a very severe, pregnancy-related disease. We recently described a novel preeclampsia mouse model by adoptively transferring activated BALB/c Th1-like splenocytes into allogeneically pregnant BALB/c female mice during late gestation. This cell transfer provoked preeclampsia symptoms (increased blood pressure and glomerulonephritis accompanied by proteinuria). Interestingly, preeclampsia-like symptoms could not be detected in nonpregnant animals receiving activated Th1-like cells. Adoptive cell transfer further affected pregnancy outcome by increasing fetal rejection through an inflammatory profile of uterine immune cells. This chapter describes the methods employed to develop the model as well as additional experiments developed to analyze cellular and molecular mechanisms involved.

Animals↗

PubMed2002

Photodynamic properties of amphiphilic derivatives of aluminum tetrasulfophthalocyanine.

Photodynamic therapy (PDT) is a promising treatment modality that has recently been accepted in clinics as a curative or palliative therapy for cancer and other nonmalignant conditions. Phthalocyanines (Pc) are attractive photosensitizers for PDT because of their enhanced photophysical and photochemical properties. The overall charge and solubility of Pc play a major role in their potential usefulness for PDT. A series of amphiphilic derivatives of tetrasulfonated aluminum Pc (AlPcS4) was prepared by substituting one of the four sulfonate groups with aliphatic side chains of 4, 8, 12 and 16 carbon atoms. The photodynamic properties of the derivatives were compared with those of AlPcS4 and the adjacent disulfonated aluminum Pc. Parameters studied included reversed-phase high-performance liquid chromatography (HPLC) retention times, capacity to generate singlet oxygen (1O2), in vitro cell uptake and phototoxicity, as well as PDT response of transplantable EMT-6 tumors in mice. The monomerized AlPcS4 derivatives showed similar or higher capacities to generate 1O2 as compared with the parent AlPcS4 as measured from relative L-tryptophan photooxidation yields. A549 cell uptake of the AlPcS4 derivatives decreased in the following order: AlPcS4(C16) > AlPcS4(C12) > AlPcS4(C8) > AlPcS4(C4). Human low-density lipoprotein at high concentrations (40 micrograms/mL) completely prevented uptake, whereas at 4 micrograms/mL uptake was decreased for the more lipophilic compounds and yet remained unaffected for the more hydrophilic dyes. Using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, A549 cell survival was assessed; it showed that photocytotoxic activity varied directly with the HPLC retention times, i.e. more hydrophilic compounds were less phototoxic. As 1O2 yields were similar for the four substituted AlPcS4 derivatives, it was postulated that the increased cytotoxic activity was caused by enhanced subcellular localization as a result of the long aliphatic side chains. These amphiphilic compounds proved to be photodynamically potent against the EMT-6 mouse mammary tumor model implanted in Balb/c mice. At dye doses of 0.2 mumol/kg and a fluence of 400 J/cm2 complete tumor regression was observed with no morbidity. The substitution of AlPcS4 with long aliphatic chains on the macrocycle greatly enhances its photodynamic efficacy both in vitro and in vivo.

Animals↗

PubMed2003

[Differentially expressed genes associated with cold acclimation].

To investigate the upregulated genes associated with cold acclimation, a cold acclimation model was established based on Balb/C mouse. mRNA of muscle and liver were isolated, and the upregulated genes of these tissues were studied by representational differential analysis (RDA). The upregulated genes then were sequenced and searched by Blast software in GenBank database. The results showed that some genes were upregulated and possibly associated with cold acclimation. Three of these genes, transferrin, fibrinogen B-beta-chains and a new gene fragment (Genbank ID: AF454762), were confirmed to be upregulated by RNA slot-blot analysis. The finding of these genes might contribute to further understanding of the molecular mechanisms of cold acclimation.

Acclimatization↗

PubMed2005

CD8+ T-cell-dependent immunity following xenogeneic DNA immunization against CD20 in a tumor challenge model of B-cell lymphoma.

The CD20 B-cell differentiation antigen is an attractive target for immunotherapy of B-cell lymphomas. In an experimental lymphoma model, BALB/c mice were immunized with mouse or human CD20 cDNA (mCD20 and hCD20, respectively) or their extracellular domains (minigenes). IFNgamma secretion by CD8+ T cells against CD20 was detected in mice vaccinated with hCD20 or human minigene, indicating that hCD20-primed CD8+ T cells recognize syngeneic CD20. Systemic challenge with syngeneic A20 cells, an aggressive lymphoma, resulted in long-term survival in a subset of immunized mice. Overall long-term survival was 14% in groups vaccinated with the human minigene versus 4% in control groups (P < 0.001). CD8+ T-cell depletion during the effector phase completely abrogated this effect. Antibodies against a recombinant mouse CD20 protein produced in insect cells were detected in mice immunized with hCD20 DNA and human and mouse minigene, but not in mice receiving mCD20 DNA. These results show that active immunization with xenogeneic DNA vaccines can induce CD8+ T cell-dependent immunity against CD20.

Animals↗

PubMed2004

Deletion of the Aspergillus fumigatus lysine biosynthesis gene lysF encoding homoaconitase leads to attenuated virulence in a low-dose mouse infection model of invasive aspergillosis.

Aspergillus fumigatus is an important pathogen of the immunocompromised host, causing pneumonia and invasive disseminated disease with high mortality. In order to determine the importance of lysine biosynthesis for growth and pathogenicity, the A. fumigatus lysF gene, encoding a homologue of the A. nidulans homoaconitase LysF, was cloned and characterized. Cosmid cosGTM encoding lysF complemented a lysF mutant of Aspergillus nidulans. A. fumigatus lysF was deleted, resulting in a lysine-auxotroph. This phenotype was complemented to the wild-type by supplementation of the medium with both L-lysine and alpha-aminoadipic acid, or transformation using cosmid cosGTM. To study the virulence of the lysF deletion mutant of A. fumigatus, a low-dose intranasal mouse infection model of invasive aspergillosis was optimized for immunosuppressed BALB/c mice, allowing the application of an infection dose as low as 5 x 10(3) conidia per mouse. In this murine model, the Delta lysF mutant was avirulent, suggesting that lysine biosynthesis, or at least a functional homoaconitase, is important for survival of A. fumigatus in vivo and a potential target for antifungal drugs.

Animals↗