Morphofunctional Characteristic of Mast Cells in BALB/c and C57Bl/6 Mice during Cold Exposure

Mast cells of the mesentery and subcutaneous tissue in BALB/c and C57Bl/6 mice were studied after single and repeated cold exposure (-20 degrees C, 3 min). Immediate adaptive reactions of mast cells in BALB/c and C57Bl/6 mice did not differ after single cold exposure and were manifested in increased degranulation. Repeated cold exposure of BALB/c mice was followed by an adaptive reaction, which included an increase in the count of mast cells in subcutaneous tissue and normalization of the degranulation index. In C57Bl/6 mice the count of mast cells in subcutaneous tissue decreased, while the degranulation index remained high. These changes reflect the disadaptive response of mast cells to repeated cold exposure.     

Comparative Characterization of Cytokine Production by Concanavalin A-Activated Splenocytes from BALB/c and C57Bl/6 Mice after Cold Exposure

The level of cytokines produced by ConA activated splenocytes was studied in male BALB/c and C57Bl/6 mice after single and repeated cold exposure (–20°C, 3 min). Single cold exposure significantly decreased IL-2, -3, -4, -5, -10, -12, IFN- production in BALB/c mice and decreased IL-2 content and increased TNF- level in C57Bl/6 mice. Repeated cold exposure normalized the content of IL-2, -4, -10, -12, and IFN- in BALB/c mice, which reflects the development of adaptive immune reactions. In C57Bl/6 mice IL-2, -3, -5, -10, -12, and IFN- production remained significantly decreased, which attested to dysadaptive processes.__________Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 139, No. 2, pp. 188–190, February, 2005     

Morphofunctional characteristic of the immune system in BALB/c and C57BL/6 mice

Inbred animals serve as an adequate model to study the role of genetic factors in adaptive, disadaptive, and pathological processes. Morphofunctional study of the immune system was performed on intact BALB/c and C57Bl/6 mice. The structural and functional parameters of the immune system in BALB/c and C57Bl/6 mice differ under physiological conditions. In BALB/c mice, volume density of T zone in the spleen and production of IL-2, IL-3, IL-4, IL-10, and TNF-α were much higher than in C57Bl/6 mice. However, IL-12 production in BALB/c mice was lower than in C57Bl/6 mice. C57Bl/6 mice were characterized by higher cytostatic activity of splenic NK cells. The observed interstrain differences are genetically determined and contribute to the type of adaptive processes and different sensitivity of these mice to pathogenic agents.     

Morphofunctional changes of BALB/c and C57BL/6 mice's immune system under chronic bacterial gram-negative endotoxicosis

Chronic endotoxicosis was modeled by subcutaneous injection of the sepharose in complex with LPS. In these conditions we have studied morphofunctional changes of the immune system of BALB/c and C57Bl/6 mice, which are characterized by the different types of the immune response (Th2 type is predominant in BALB/c, Th1--in C57Bl/6). In the 1st-7th day t in the serum of BALB/c mice the endotoxin level increased in 21.3 times, in C57Bl/6--in 20.6 times. The endotoxin antibodies significantly decreased in 1th-7th days, on the 14th day it increased in the serum of both mice's strains. Morphofunctional changes of the immune system after chronic endotoxicosis were different in BALB/c and C57BI/6 mice. On the 1th day after injection of LPS and sepharose, in the thymus of C57Bl/6 mice the cortex layer was exhausted because of cell death, in the thymus of BALB/c mice II-III stages of accidental involution were developed. On the 7-14th day after injection of LPS and sepharose in the spleen of C57Bl/6 mice T- and B-zones were hyperplastic, however in spleen of BALB/c mice only T-zone were enlarged. After LPS and sepharose injection changes of cytokine production synthesized by KonA activated splenic cells were found out. In both strains the level of proinflammatory cytokines--TNFalpha and IL-1beta decreased, as well the Th1-cytokine IL-2. The production o fTh2-cytokine - IL-4, significantly decreased only in C57BI/6 mice. We suggest that damaging effect of LPS injection is determined by predominant Th2 or Th2 types of the immune response.     

BALB/c and C57Bl/6 mice infected with virulentBurkholderia pseudomalleiprovide contrasting animal models for the acute and chronic forms of human melioidosis

Burkholderia pseudomalleiis the aetiological agent of melioidosis, a life-threatening bacterial disease occurring in many species of animals, including man. Infection in humans commonly manifests as one of three clinical presentations: acute, subacute or chronic disease. Investigations were undertaken to assess the suitability of BALB/c and C57Bl/6 mice as animal models for the different forms of human melioidosis. The course of infection in BALB/c mice was similar to that which occurs in acute human infection. By contrast, infection of C57Bl/6 mice appeared to mimic chronic human melioidosis. While BALB/c mice suffered a rapidly-progressive bacteraemia which resulted in host death by 96 h, C57Bl/6 mice were able to prevent this, and typically remained asymptomatic for up to 6 weeks. LD₅₀values of 4 cells and 2.5×10⁴cells for BALB/c and C57Bl/6 mice, respectively, reflect these observations. The heightened level of resistance toB. pseudomalleiobserved in C57Bl/6 mice was suggested to have a genetic basis, when the susceptibilities of first filial and reciprocal backcross generations were examined. Growth kinetics ofB. pseudomalleiwithin BALB/c and C57Bl/6 peritoneal exudate cell (PEC) cultures were examined to investigate PEC microbicidal efficiency as a determinant of host susceptibility. C57Bl/6 PEC cultures exhibited greater microbicidal efficiency towardsB. pseudomalleiwhen compared to BALB/c cells, indicating that susceptibility may be determined by non-specific, cellular mechanisms. Collectively, these results suggest that the BALB/c and C57Bl/6 strains of mice may provide excellent models for acute and chronic human melioidosis, respectively.     

Effect of dioxydine and cyclophosphane on lipid peroxidation and superoxide dismutase and catalase activities in C57Bl/6 and BALB/c mice

Twenty-four hours after intraperitoneal injection of cyclophosphane (40 mg/kg) and dioxydine (300 mg/kg) to C57Bl/6 mice, liver catalase activity dropped by 29 and 23%, respectively. In BALB/c mice, dioxydine (but not cyclophosphane) reduced catalase activity by 24%. Superoxide dismutase activity was lowered by cyclophosphane (but not dioxydine) in BALB/c mice, and by both dioxydine and cyclophosphane in C57Bl/6 mice (by 24 and 86%, respectively). The level of 2-thiobarbituric acid (TBA)-reactive lipid peroxidation (LPO) products in the liver of BALB/c mice treated with cyclophosphane and dioxydine increased 1.4- and 2.1-fold, respectively, while in C57Bl/6 mice it did not differ from the control. The initial rate ofin vitro-induced LPO in BALB/c mice receiving cyclophosphane and dioxydine increased 1.5- and 4-fold, respectively. In C57Bl/6 mice both cyclophosphane and dioxydine inhibited the accumulation of TBA-reactive LPO products. On the whole, animals of the C57Bl/6 strain are more resistant to the LPO-inducing action of mutagens than BALB/c mice, despite the fact that the latter are characterized by a higher activity of antioxidant enzymes. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, No. 5, pp. 528–532, May, 1996     

Benzodiazepine Reception in C57Bl/6 and BALB/c Mice Depending on the Type of Stress Factor

Specific binding of ³Н-fl unitrazepam with synaptosomal membranes after exposure to open field test and “contact with predator” test was measured in C57Bl/6 and BALB/c mice. Stress-induced decrease in benzodiazepine binding after open field test was observed only in BALB/c mice and after contact with predator in both animal strains.     

Differences in migration inhibitory factor production by C57Bl/6 and BALB/c mice in allergic and irritant contact dermatitis

Two strains of mice, BALB/c and C57Bl/6, which are known to differ in their inflammatory responsiveness to allergens, were analyzed regarding their expression of macrophage migration inhibitory factor (MIF). Allergic contact dermatitis to 2,4-dinitro-1-fluorobenzene and irritant contact dermatitis to croton oil were studied immunohistologically at designated time intervals after elicitation. BALB/c mice presented a significantly more intense ear swelling response than C57Bl/6 mice and showed a strong endothelial MIF expression in the early phase of inflammation in both allergic and irritant contact dermatitis. Endothelial MIF expression was much weaker in C57Bl/6 mice. Furthermore, the infiltration rate of inflammatory cells (MIF+ and BM8+ macrophages, Lyt2+ and L3T4+ T cells) was significantly higher in BALB/c than in C57Bl/6 mice. We conclude that genetically determined differences of susceptibility to allergens and irritants in BALB/c and C57Bl/6 mice are reflected by the intensity of MIF expression in the microvascular endothelium and immigrating inflammatory cells. MIF seems to appear as first molecular equivalent of developing inflammation and probably determines the degree of cellular infiltration.     

Tryptophan hydroxylase 2 genotype determines brain serotonin synthesis but not tissue content in C57Bl/6 and BALB/c congenic mice

Tryptophan hydroxylase 2 (TPH2) catalyzes the rate-limiting step in the synthesis of brain serotonin (5-HT). In a previous report, a single nucleotide polymorphism in mTph2 (C1473G) reduced 5-HT synthesis by 55%. Mouse strains expressing the 1473C allele, such as C57Bl/6, have higher 5-HT synthesis rates than strains expressing the 1473G allele, such as BALB/c. Many studies have attributed strain differences to Tph2 genotype without ruling out the potential role of alterations in other genes. To test the role of the C1473G polymorphism in strain differences, we generated C57Bl/6 and BALB/c mice congenic for the Tph2 locus. We found that the 1473G allele reduced 5-HT synthesis in C57Bl/6 mice but had no effect on 5-HT tissue content except for a slight reduction (15%) in the frontal cortex. In BALB/c mice, the 1473C allele increased 5-HT synthesis but again did not affect 5-HT tissue content. At the same time, 5-hydroxyindoleacetic acid (5-HIAA) was significantly elevated in BALB/c congenic mice. In C57Bl/6 mice, there was no effect of genotype on 5-HIAA levels. BALB/c mice had lower expression of monoamine oxidase A and B than C57Bl/6 mice, but there was no effect of Tph2 genotype. On the tail suspension test, escitalopram treatment reduced immobility regardless of genotype. These data demonstrate that the C1473G polymorphism determines differences in 5-HT synthesis rates among strains but only minimally affects 5-HT tissue levels.     

Age-related changes in dermal mast cell prevalence in BALB/c mice: functional importance and correlation with dermal mast cell expression of Kit

Differences in dermal mast cell prevalence for adult mice of different strains have been reported previously. In this study, the dermal mast cell prevalence for BALB/c and C57BL/6 mice at 6 weeks of age was similar but as BALB/c mice matured from 6 to 10 weeks of age, their dermal mast cell prevalence halved. In contrast, there was no significant difference in the dermal mast cell prevalence of 6- and 10-week-old C57BL/6 mice. These differences determined the degree of susceptibility of BALB/c and C57BL/6 mice of different ages to UVB (UV radiation of wavelength 280-320 nm)-induced systemic immunosuppression. Expression of the receptor for stem cell factor, Kit protein, was examined on mast cells under conditions in which the dermal mast cell prevalence varied. A significant correlation was observed between Kit expression by mast cells from adult BALB/c, DBA/2 and C57BL/6 mice and dermal mast cell prevalence. In BALB/c mice, mast cell Kit expression decreased as the mice matured from 6 to 10 weeks of age and correlated with the reduction in dermal mast cell numbers. Kit levels on dermal mast cells from C57BL/6 mice were consistently higher than on mast cells from BALB/c mice although significant reductions in Kit were also measured with ageing from 6 to 10 weeks. We hypothesize that regardless of the extent of Kit expression, the dermal mast cell populations were maximally expanded in C57BL/6 mice. We suggest that BALB/c mice of 6 and 10 weeks of age are useful hosts in which to quantitatively evaluate mast cell involvement in a range of functional assays involving skin.     

Immunity Parameters in Mice of Different Strains

Quantitative composition and functional activity of immunocompetent cells differ in mice of different strains. The counts of T cells in the bone marrow and spleen, proliferative activity of T cells in the spleen, levels of IL-2 and IL-10 production by splenic T cells, number of antigen-specific T cells and their functional activity are low in C57Bl/6, BALB/c, and CC57W mice and high in CBA/CaLac, DBA/2, and C3H animals. Low phagocytic activity of peritoneal macrophages was detected in BALB/c and CC57W mice and high activity in C3H animals. The content of antibody-producing cells in the spleens of C57Bl/6, BALB/c, and CC57W mice is higher than in CBA/CaLac, DBA/2, C3H, A/SN, and AKR/JY mice. Functional activity of B cells is lower in BALB/c and CC57W compared to CBA/CaLac and DBA/2 mice. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 140, No. 8, pp. 189–191, August, 2005     

Naloxone Effects on Behavior of Inbred Mice with Different Response to Emotional Stress in Open Field Test

Effects of nonspecific opiate receptor antagonist naloxone in doses of 0.1, 0.5, 1.0, 5.0, 10.0 mg/kg on open field behavior and spontaneous motor activity were studied in male BALB/c and С57Bl/6 mice. Differently directed effects of naloxone on behavioral parameters of emotional-stress reaction in BALB/c and С57Bl/6 mice were observed. Naloxone increased motor activity in the open field test in BALB/c mice, but decreased it in С57Bl/6 mice. In the absence of stress, naloxone in the studied dose range did not affect spontaneous motor activity in С57Bl/6 mice, and significantly reduced activity in BALB/c mice in doses 0.5 and 1.0 mg/kg.     

Quantitative and qualitative differences in bronchoalveolar inflammatory cells in Pseudomonas aeruginosa-resistant and -susceptible mice

The difference in severity of Pseudomonas aeruginosa-induced chronic lung infection may be determined by differences in host inflammatory responses. In the present study we investigate this possibility using BALB/c and C57Bl/6 mice, resistant and susceptible, respectively, to chronic lung infection with P. aeruginosa. Following intratracheal inoculation of P. aeruginosa-impregnated agar beads, C57Bl/6 mice mounted a stronger inflammatory response with significantly higher total cell numbers in the bronchoalveolar lavage fluid compared with BALB/c mice. While polymorphonuclear leucocytes were the predominant cell in C57Bl/6 mice, macrophages constituted the majority in BALB/c mice at day 7 post-infection. Alveolar macrophages from C57Bl/6 mice showed significantly higher spontaneous production of nitric oxide (NO) at day 7 post-infection compared with BALB/c mice. Following in vitro stimulation with heat-killed Pseudomonas antigen, these cells produced significantly higher NO compared with cells from BALB/c mice at day 21 post-infection. Production of tumour necrosis factor-alpha (TNF-α) by alveolar macrophages was significantly higher at day 7 in BALB/c mice compared with C57Bl/6 mice, which showed significantly higher levels at day 28 post-infection. Taken together, these results suggest that defects in the host inflammatory process contribute to the variable outcome of chronic lung infection with P. aeruginosa. An exaggerated inflammatory response dominated by polymorphonuclear cells correlates with susceptibility to infection, whilst a modest inflammatory response dominated by macrophages correlates with resistance. Moreover, the quantity and timing of production of NO and TNF-α by alveolar macrophages may modulate the course and outcome of infection.     

Antioxidant enzymes and lipid peroxidation in C57Bl/6 and BALB/c mice

Superoxide dismutase and catalase activities and levels of thiobarbituric acid-reactive lipid peroxidation (LPO) products were estimated in the liver of C57B1/6 and BALB/c mice. The results indicate that although antioxidant enzymes are more active in BALB/c mice, compensation of oxidation processes in this strain is possible only if LPO-inducing agents are absent or present at low levels, and that these agents, including exogenous ones, may be expected to activate lipid oxidation in this strain to a greater extent than in C57Bl/6 mice. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 12, pp. 580–583, December, 1995     

Mouse models of asthma: a comparison between C57BL/6 and BALB/c strains regarding bronchial responsiveness, inflammation, and cytokine production

Objective

Animal models of asthma mimic major features of human disease. Since the genetic background of experimental animals might affect hyperresponsiveness and inflammation, we studied its potential influence and the mechanisms leading to differences in strains.

Methods

We applied a mouse model of allergic asthma to BALB/c and C57BL/6 mice.

Results

BALB/c mice displayed greater levels of airway reactivity to methacholine than C57BL/6 mice. Moreover, BALB/c mice exhibited higher numbers of mast cells in lung tissue when compared to C57BL/6. On the contrary, eosinophil and neutrophil counts in bronchoalveolar lavage fluid (BALF) as well as peribronchial eosinophilia were greater in C57BL/6. IL (Interleukin)-4, IL-5, IL-13, and CCL11 levels measured in whole-lung extracts were higher in BALB/c, while, in sharp contrast, CCL11 and CCL5 levels were higher in BALF of C57BL/6 mice.

Conclusions

We observed phenotypic differences between C57BL/6 and BALB/c mice in an asthma model with different distributions of pro-inflammatory cytokines and inflammatory cells.     

Mast cells at the host-pathogen interface: host-protection versus immune evasion in leishmaniasis

Infection of a susceptible host with Leishmania, a protozoan parasite, causes the disease leishmaniasis, which is characterized by neutrophil, eosinophil, macrophage, lymphocyte and mast cell infiltration into the infected tissue followed by parasite growth. Although the roles played by other cells in leishmaniasis are known, the role of mast cells remains to be ascertained. Here, we demonstrate that Leishmania regulates mast cell infiltration to the site of infection, mast cell production and mast cell function resulting in differential growth of the parasite in resistant (C57BL/6 or CBA/T6T6) and susceptible (BALB/c) macrophages. An interleukin-3-dependent augmentation in mast cell committed progenitors is observed in BALB/c but not in C57BL/6 mice during Leishmania infection. The mast cell supernatants inhibit IFN-gamma-dependent restriction of Leishmania growth in macrophages in BALB/c mice whereas the reverse phenomenon occurs in C57BL/6 mice. Our data reveals a different facet of host-pathogen interaction.     

Endothelial cells and renal epithelial cells do not express the Wegener''s autoantigen, proteinase 3.

In vitro and in vivo T cell responses were determined during the course of bronchopulmonary infection with mucoid Pseudomonas aeruginosa. T cell responses were compared in two inbred mouse strains, namely BALB/c mice, which are resistant to the establishment of chronic bronchopulmonary Ps. aeruginosa infection, and C57Bl/6 mice, which have high numbers of bacteria in the lungs through 14 days post-infection. Unseparated lung cells and lung T cells from BALB/c mice exhibited significantly higher in vitro proliferative responses to both heat-killed Ps. aeruginosa and concanavalin A (Con A) than cells from C57Bl/6 mice through 20 days post-intratracheal infection with 10(4) colony-forming units (CFU) Ps. aeruginosa. Proliferation of unseparated lung cells but not lung T cells from BALB/c mice infected 6 days previously with 10(5) CFU Ps. aeruginosa was suppressed in response to Con A; these cells were unresponsive to specific antigen. Suppression of lymphocyte proliferation in the lungs of C57Bl/6 mice infected with 10(4) CFU Ps. aeruginosa and in BALB/c mice infected with 10(5) CFU was found to be mediated by adherent lung cells via the production of nitric oxide and prostaglandins. Determination of in vivo T cell-mediated responses in infected mice demonstrated that resistant BALB/c mice had high DTH and low Pseudomonas-specific antibody responses, while C57Bl/6 mice had low DTH and high antibody levels, in particular, IgG2b and IgM.     

Immune alterations induced by chronic noise exposure: Comparison with restraint stress in BALB/c and C57Bl/6 mice

Abstract

Exposure to loud noise levels represents a problem in all regions of the world. Noise exposure is known to affect auditory structures in living organisms. However, it should not be ignored that many of the effects of noise are extra-auditory. In particular, it has been proposed that noise could affect immune system similarly to other stressors. Nevertheless, only a few studies so far have investigated the effects of noise on the immune function. The aim of the present work was to investigate the effect of chronic (2 weeks) noise (95–97?dBA) exposure on immune responses in BALB/c and C57 mice. To ascertain if the effect of noise is similar to other psychological stressors, the effect of chronic restraint—applied for the same time—on immune response was also analyzed. It was found that chronic noise impaired immune-related end-points in vivo and ex vivo depending on the strain used. Noise, but not restraint, affected C57Bl/6 mouse T-cell-dependent antibody production and ex vivo stimulated T-cell proliferation, but had no effect on these parameters in BALB/c mice or their cells. In fact, none of the stressors altered T-cell responses associated with the BALB/c mice. Further, noise exposure induced a decrease in corticosterone and catecholamines levels in BALB/c mice. In contrast, no differences were seen in these parameters for those BALB/c mice under restraint or for that matter C57Bl/6 mice exposed to restraint or noise. The results of these studies indicate that noise could seriously affect immune responses in susceptible individuals. In addition, it may also be concluded that noise possibility should not be considered a classic stressor.     

Experimental African trypanosomiasis: differences in cytokine and nitric oxide production by macrophages from resistant and susceptible mice.

Immunosuppression in experimental infections with Trypanosoma congolense is mediated by the synergistic action of macrophages and a novel lymphocyte(s), which involves the activity of IFN-gamma as well as IL-10. BALB/c mice are highly susceptible while C57Bl/6 mice are relatively resistant to T. congolense infections. Plasma and/or supernatants of spleen cell cultures of infected susceptible BALB/c mice have more IL-10 but less IL-12 than those of infected relatively resistant C57Bl/6 mice. Cells of a BALB/c macrophage cell line, when pulsed with T. congolense, produce more IL-10 and IL-6, but have less TNF-alpha mRNA, than equally treated cells of a C57Bl/6 cell line. Peritoneal and/or bone marrow-derived macrophages obtained from BALB/c mice, pulsed with T. congolense in culture, produce less nitric oxide, TNF-alpha and IL-12, but more IL-6 and IL-10 than equally treated macrophages isolated from C57Bl/6 mice. We suggest that genetic resistance to African trypanosomiasis is expressed at the level of the macrophage.     

Spontaneous expression of endogenous type C RNA virus by BALB/c splenic B lymphocytes in continuous culture.

B-lymphocyte cultures were established from spleens of BALB/c, C57B1/6, NIH Swiss, and SWR mice of various age groups. Spontaneous, consistent, and thus predictable release of a B-tropic mouse endogenous virus occurred from the very first passage in cultured lymphocytes derived from BALB/c mice 6 months old or older but not from similar lymphocytes derived from BALB/c mice of 1.5 or 3 months of age. C57Bl/6, NIH Swiss, and SWR mice belonging to various age groups ranging between 1.5 and 18 months failed to exhibit such a spontaneous release of viral particles. We conclude that in BALB/c splenic B lymphocytes a breakdown of cellular control mechanisms occurs in older animals leading to viral production while such a phenomenon is absent in C57Bl/6, NIH Swiss, and SWR mice.