No priming of the immune response in newborn brown norway rats dosed with ovalbumin in the mouth

BACKGROUND: Other researchers have reported that the specific immune response to subsequent antigen challenge is primed in newborn mice or rats dosed orally by gavage. We wanted to investigate if priming of a subsequent specific IgE response could be achieved by dosing newborn rats orally with ovalbumin and if this method could be used in an animal model for food allergy. METHODS: Newborn Brown Norway rats were dosed with ovalbumin in the mouth (100 microg or 6 mg). As young adults, the animals were dosed by gavage for 35 days with 1 mg ovalbumin/day or once intraperitoneally with 100 microg. Control groups were dosed by gavage or intraperitoneally but not as neonates. Additionally, young adult rats were dosed with 1 mg ovalbumin/day in the mouth for 35 days. Sera from individual animals were analysed for specific IgE and specific IgG. RESULTS: In all experiments with neonatal rats the specific IgE and IgG responses were decreased compared to the control groups, however, not always reaching statistical significance. A statistical significant decrease in the specific immune response was found in young adult rats dosed in the mouth as compared to by gavage. CONCLUSIONS: Dosing Brown Norway rats with ovalbumin in the mouth as neonates do not prime the specific immune response. The decrease in immune response found in our experiments when dosing newborn animals in the mouth in opposition to the priming seen by others when dosing by intragastric intubation may be explained by a dissimilar antigen presentation when dosing includes both oral mucosa and gut.     

Allergen-induced airway remodeling in brown norway rats: structural and metabolic changes in glycosaminoglycans

Increased proteoglycan (PG) deposition is a feature of airway remodeling in asthma. Glycosaminoglycans (GAGs) mediate many of the biological and mechanical properties of PGs by providing docking sites through their carbohydrate chains to bioactive ligands; therefore, it is imperative to define structural and metabolic changes of GAGs in asthma. Using a Brown Norway (BN) ovalbumin (OVA)-sensitized and -challenged rat model to induce airway remodeling, we found excessive deposition of chondroitin/dermatan (CS/DS)-, heparan (HS), and keratan (KS) sulfate GAGs in the airways and bronchoalveolar lavage cells of OVA-challenged rats. Disaccharide composition of CS/DS of OVA-challenged rats was significantly different compared with saline-treated (SAL) control rats, with increased levels of 0-, 6-, and 4-sulfated disaccharides. Increases in the amount and a change in the proportion of CS/DS versus HS GAGs were noted in OVA-challenged rats. The higher content and sulfation of CS/DS disaccharides was reflected by the increased expression of xylosyltransferase-I, β1,3-glucuronosyltransferase-I, chondroitin-4, and chondroitin-6 sulfotransferase genes and protein expression of xylosyltransferase-I and β1,3-glucuronosyltransferase-I in OVA-challenged rats. Genes encoding the core proteins of the CS/DS and KS-containing PGs, such as versican, biglycan, decorin, and lumican, were overexpressed in OVA-challenged rats. Our results suggest that GAG biosynthetic enzymes may be involved in the altered expression of GAGs in the airways and are potential targets for inhibiting excess PG-GAG deposition and the airway remodeling process in asthma.     

Effects of diesel exhaust particles and carbon black on induction of dust mite allergy in brown norway rats

Particulate matter (PM) components of air pollution have been associated with mortality and health risks in susceptible populations including asthmatics. More than a decade of PM research has demonstrated that these effects do not occur indiscriminately and are related to particle size, surface area, and chemical composition. Experimental evidence in rodents indicates that inhaled or instilled diesel exhaust particles (DEPs) increase lung injury, inflammation, and allergic airway responses, and that ultra-fine carbon black (UFCB) particles cause more pulmonary inflammation than fine carbon black (FCB) particles in a dose-dependent manner. Our preliminary work determined that a dose of 100 mug of FCB, UFCB, or DEPs (NIST SRM 2975) was sufficient to enhance pulmonary inflammation in Brown Norway (BN) rats 24 hours after intratracheal (IT) instillation of the particles. In the current investigation, we sought to compare, on a mass basis, the effects of a 100 mug dose of these particles on allergic sensitization to house dust mite (HDM) antigen. Immediate airway responses (IAR) to HDM challenge and a battery of proinflammatory, allergic, and acute injury responses in the lung were then measured two and seven days post-challenge. DEPs exposure increased 8 of 10 responses including IAR and levels of IL-4, IL-13, TNFalpha, total protein, cysteinyl leukotrienes, and eosinophils in bronchoalveolar lavage fluid (BALF). UFCB and FCB significantly enhanced 4 of 10 and 2 of 10 of these responses compared to saline, respectively. Among other responses that were not statistically elevated with particle treatment, mean values for FCB were higher than for UFCB. Particles administered prior to challenge rather than prior to sensitization did not significantly enhance any of these responses above levels of saline controls. We conclude that on a mass basis, DEPs had the greatest potential to enhance allergic induction, indicating that chemical composition is more important than particle size in determining potency for this health effect.     

Studies of social learning in norway rats: A brief review

I review below some of the research on social learning in Norway rats carried out in my laboratory from 1969 to 1980. Two independent lines of research are discussed; both involve analysis in the laboratory of possible instances of social learning first described by observers of free-living, wild rats. The 1st research program analyzes social interactions important in the transmission of learned food preferences from adult rats to their young. The 2nd examines the possibility that the habit of diving in shallow water for food is socially transmitted from 1 rat to another.     

Inflammatory and immune mechanisms in contact hypersensitivity (CHS) in rats

Contact hypersensitivity (CHS) is a T-cell-mediated skin inflammatory reaction to cutaneous exposure to small sensitizing chemicals, haptens. Majority of CHS studies were conducted in mice and there is paucity of data in other experimental animals. In this review, after a brief survey of murine CHS, hitherto known characteristics of CHS in rats were presented including inflammatory and immune mechanisms of both sensitization and elicitation phases. Survey of literature of rat CHS is presented, with our data concerning the importance of genetic background both in the induction and in the expression of reaction to dinitrochlorobenzene. The knowledge of CHS in rats, preferred animal in immunopharmacological studies, might help development of immunomodulatory intervention in contact allergy.     

他汀类药物对免疫细胞功能的调节作用及机制

他汀类药物是羟甲基戊二酸单酰辅酶A(HMG-CoA)还原酶的抑制剂,因其显著的降脂功能而广泛应用于治疗动脉粥样硬化和心血管疾病.近年来研究发现,他汀类药物在CD4+T细胞介导的多种自身免疫性疾病中显示了免疫调节功能,可有效预防和治疗这类疾病.本文将对他汀类药物的免疫调节功能及潜在机制进行初步的探讨.     

Beneficial effects of rosuvastatin on aortic adverse remodeling in nitric oxide-deficient rats

This study aimed to evaluate the effect of rosuvastatin upon structural and ultrastructural aortic remodeling in a rat model of hypertension induced by NO synthase blockade. Wistar rats were divided into 4 groups: Control group (C); control treated with rosuvastatin 20 mg/kg/day (CR); L-NAME group 40 mg/kg/day (LN) and L-NAME treated with rosuvastatin (LNR) (same doses). Body mass and blood pressure were measured weekly; the experiment lasted 5 weeks. L-NAME administration augmented blood pressure (BP) in the LN group in comparison to the C group (123.3 vs. 180.5 mmHg at week 5). In LNR rats, rosuvastatin slightly attenuated BP rise, but it had no effect on the BP of CR group. Intima and media thickening of the thoracic aorta were observed in the LN group, and increased elastic fiber content as well. Rosuvastatin prevented all these alterations as seen in the LNR group. Ultrastructural changes due to L-NAME intake (intracellular vesicles and altered membrane morphology in endothelial cells, extracellular matrix deposition, and cytoplasmatic projections from smooth muscle cells toward the internal elastic lamina) were also prevented by rosuvastatin. All in all, rosuvastatin administration is capable of attenuating ultrastructural aortic wall remodeling in NO-deficient rats despite small changes in blood pressure.     

Respiratory effects of sensorimotor cortex and their mechanisms in rats

Acute experiments on anesthetized rats showed differential effect of various areas of the sensorimotor cortex on activity of the respiratory center. It is hypothesized that GABAergic structures of the solitary tract nucleus play an important role in the mechanisms of respiratory effects of the sensorimotor cortex.     

Studies on the formation of glomerular immune deposits in brown Norway rats injected with mercuric chloride

Brown Norway rats injected with mercuric chloride (HgCl2) develop autoantibodies which immunolocalize along the glomerular basement membrane at first in a linear pattern and then in a granular pattern. The aim of this study was to characterize the specificity of these antibodies and to investigate the mechanisms responsible for the formation of granular immune deposits in the subepithelial zone of the glomerular basement membrane. The rats were found to develop circulating anti-laminin, anti-type IV collagen, anti-heparan sulfate proteoglycan, and anti-entactin antibodies. Antibodies against laminin and type IV collagen were found in relatively high titers in the sera and were specifically concentrated in the nephritic kidneys. Antibodies eluted from the nephritic kidneys with either linear or granular deposits reacted with basement membrane antigens synthesized and secreted by cultured rat glomerular visceral epithelial cells. Thus, in this model, the interaction of anti-laminin and type IV collagen antibodies with antigens secreted by glomerular visceral epithelial cells might, together with other mechanisms, contribute to the formation of granular immune deposits in the subepithelial part of the glomerular basement membrane.     

Chronic effects of clozapine administration on insulin resistance in rats: Evidence for adverse metabolic effects

Chronic treatment with the atypical antipsychotics clozapine has been associated with an increased risk for deterioration of glucose homeostasis, leading to hyperglycemia and insulin resistance diabetes. The present study mainly aimed to investigate possible mechanisms underlying clozapine-induced hyperglycemia. Male Wistar albino rats were randomly divided into two groups (each consists of 12 rats). The first group received clozapine orally at a dose of 10 mg/kg body weight daily for 6 weeks, while the other group received the drug vehicle only and served as the control group. At the end of the six weeks, hyperglycemia, hyperinsulinemia and insulin resistance, as indicated by Homeostatic model assessment of insulin resistance (HOMA-IR), were observed in the clozapine group as compared with the control group. This disturbance in glucose regulation was associated with non-significant changes in body weight, serum cortisol level, and hepatic glycogen content. The Clozapine group showed a significant increase in hepatic phosphorylase activity and in the gene expression level of hepatic glucose-6-phosphatse (G6Pase) enzymes compared to the control group. It can be concluded that clozapine-induced hyperglycemia and insulin resistance occur in a manner mostly independent of weight gain, and may be attributed to an increase in hepatic phosphorylase activity and increased expression level of G6Pase.     

山茱萸总苷抗炎免疫抑制作用及其机理的大鼠实验研究

目的 研究山茱萸总苷（COG）对大鼠佐剂性关节炎（AA）的作用及其机理。方法 采用弗氏完全佐剂形成大鼠AA模型，于造模后不同时间分别测定两侧足趾肿胀度，造模24d后，处死动物观察药物对踝关节组织病理的影响，对T淋巴细胞增殖、炎性细胞因子IL-1、TNF-a、IL-6及迟发型超敏反应（DTH）、前列腺素E2（PGE2）的作用。结果 COG对AA大鼠的原发病变和继发病变均有明显的治疗作用（P〈0.01），对造模引起的踝关节组织病理损伤有明显的改善，且明显抑制从大鼠的T淋巴细胞增殖反应和DTH（P〈0.01），抑制IL-1、TNF-a、IL-6等炎性细胞因子及血浆PGE2的产生（P〈0.01或P〈0.05）。结论COG具有较好的免疫抑制抗炎作用，其机理可能是抑制了炎性介质IL-1、IL-6、TNF-a和PGF2的产生。     

头孢噻甲羧肟对肺炎大鼠免疫应答的调节作用

目的 初步探讨了头孢噻甲羧肟（ＣＡＺ）对肺炎大鼠的免疫调节作用。方法;雄性Ｗｉｓｔａｒ大鼠采用气管内注入感染法制备肺炎克雷伯氏杆菌性肺炎模型,注射治疗剂量ＣＡＺ７ｄ后测定免疫指标：结果ＣＡＺ增强巨噬细胞的吞噬功能及ＡＤＣＣ活性;降低ＣＤ４＾＋Ｔ淋巴细胞亚群,对脾小结发生中心Ｂ细胞密度,ＰＭＮ－ＣＬ及巨噬细胞ＡＣＰ活性无影响,结论：ＣＡＺ可增强肺炎大鼠巨噬细胞和抑制Ｔ淋巴细胞的免疫应答反应。     

Complement-mediated immune mechanisms in allergy

Allergic conditions are associated with canonical and noncanonical activation of the complement system leading to the release of several bioactive mediators with inflammatory and immunoregulatory properties that regulate the immune response in response to allergens during the sensitization and/or the effector phase of allergic diseases. Further, immune sensors of complement and regulator proteins of the cascade impact on the development of allergies. These bioactive mediators comprise the small and large cleavage fragments of C3 and C5. Here, we provide an update on the multiple roles of immune sensors, regulators, and bioactive mediators of complement in allergic airway diseases, food allergies, and anaphylaxis. A particular emphasis is on the anaphylatoxins C3a and C5a and their receptors, which are expressed on many of the effector cells in allergy such as mast cells, eosinophils, basophils, macrophages, and neutrophils. Also, we will discuss the multiple pathways, by which the anaphylatoxins initiate and control the development of maladaptive type 2 immunity including their impact on innate lymphoid cell recruitment and activation. Finally, we briefly comment on the potential to therapeutically target the complement system in different allergic conditions.     

动脉粥样硬化发生的免疫学机制

在动脉粥样硬化形成发展中,有大量与免疫相关的细胞参与并形成了一系列免疫反应机制,主要包括:免疫系统的单核,巨噬细胞和淋巴细胞、内皮细胞、平滑肌细胞等,它们在各种免疫分子的协调下相互作用,相互影响,共同参与了动脉粥样硬化的发生、发展。     

Mother-weanling interactions in norway rats in the presence of a successive litter produced by postpartum mating

When female Norway rats (Rattus norvegicus) become pregnant at the postpartum estrus they nurse this first litter concurrently with the gestation of a second litter. This second gestation is of variable length (23–31 days in this study) We investigated the behavior of mothers and their older litters around the time the second litter was born. Six female rats gave birth and were mated at the postpartum estrus. Continuous videotaped observation of each female and litter began approximately 3 days before, and continued for 3 days after the birth of the second litter. We found that suckling behavior and nest attendance by the older litter did not necessarily end when the second litter was born. When the gestation length of the second litter was short (23–25 days) older pups continued to spend time in the nest and to nurse along with their newborn siblings. These older pups also spent much time on the nest even in the absence of their mother. When gestation was long (27–31 days) older pups were weaned before the birth of the second litter and spent less time on the nest with the newborns. Stereotyped attacks by the female against her weanling age pups were seen both pre- and postpartum. This maternal aggression did not appear to deter suckling and nest attendance by the weanlings.