scholarly journals MATERNALLY INDUCED TRANSPLANTATION IMMUNITY, TOLERANCE, AND RUNT DISEASE IN RATS

1972 ◽  
Vol 135 (4) ◽  
pp. 808-826 ◽  
Author(s):  
Alan E. Beer ◽  
R. E. Billingham ◽  
S. L. Yang

A previous report that the offspring of outbred Sprague-Dawley rats, born of mothers presensitized or tolerant with respect to tissue antigens of the Lewis strain, and reinoculated with Lewis cells during their pregnancy, reject test grafts of Lewis skin in an accelerated manner has been confirmed. This "maternally induced" alteration in reactivity of the progeny has been found to be long lasting, immunologically specific, and probably not due to transfer of humoral antibody. It has been established that the reexposure of the mothers to donor cellular antigen during pregnancy augmented the influence of the prior states of tolerance or sensitivity. To obviate the complications inherent in working with the outbred Sprague-Dawley rats, the key experiments summarized above were repeated with isogenic Fischer rats as parents and Lewis rats as the tissue donors as before. With this combination it was found that a state of prior sensitization or tolerance in the mothers resulted in the apparent induction of tolerance in some of their progeny. Reinoculation of either the tolerant or sensitized mothers during pregnancy slightly increased the incidence and degree of impairment of their offsprings' capacity to reject Lewis skin grafts. A single intraperitoneal injection of 100 x 106 million Lewis lymphoid cells into normal Fischer rats in the 14th–16th day of pregnancy also weakened the reactivity of their progeny to Lewis test grafts. Further to test the premise that this weakened reactivity might be due to maternal induction of tolerance, by antenatal transmission of alien cells, the lymphohematopoietic tissue system of adult Fischer females was replaced by that from Lewis donors with the aid of cyclophosphamide. It was anticipated that when these animals were mated with Fischer males, sufficient Lewis leukocytes might cross the placentas to induce high degrees of tolerance. Although normal sized healthy litters were born, about 50% of the infants succumbed to graft-versus-host (GVH) or runt disease within 40 days, many of them giving evidence of being tolerant of Lewis grafts. The mothers, too, developed chronic GVH disease. The offspring of Fischer females made chimeric with cells from (Fischer x Lewis)F1 hybrid donors, as well as their mothers, remained healthy. Intraperitoneal injection of normal Fischer females, in the 15th–17th day of pregnancy, with 100 million lymphoid cells from specifically sensitized Lewis rats, also caused fatal runt disease to develop in about 50% of their offspring, but left the mothers unscathed. Taken together, these various findings indicate that in some genetic contexts at least the extent of the natural surreptitious transplacental cellular traffic can be considerably augmented experimentally, though how this comes about and why lymphocytic cells that are foreign to the mother can apparently gain access to fetuses more readily than her own cells remain to be determined.

1994 ◽  
Vol 267 (2) ◽  
pp. R502-R507 ◽  
Author(s):  
H. Sidransky ◽  
E. Verney

Since Lewis rats are susceptible to many inflammatory diseases and have been used in an experimental model of the eosinophilia-myalgia syndrome, we investigated whether Lewis rats would respond to L-tryptophan as have Sprague-Dawley rats reported earlier. In this comparative study using females of both strains, we observed a decrease in the affinity of in vitro L-tryptophan binding to hepatic nuclei and nuclear envelopes of Lewis rats compared with Sprague-Dawley rats. However, in vivo stimulatory effects of administering L-tryptophan on hepatic polyribosomal aggregation, protein synthesis, and nuclear RNA release were similar in both strains. In vitro [3H]tryptophan binding to hepatic nuclear envelopes, using L-tryptophan implicated in cases of the eosinophilia-myalgia syndrome, revealed less specific binding than when using nonimplicated L-tryptophan in both strains. The possible significance of the quantitative difference in the binding affinity of L-tryptophan to hepatic nuclei of Lewis rats compared with those of Sprague-Dawley rats is as yet undetermined.


2021 ◽  
Vol 21 (12) ◽  
pp. 6205-6211
Author(s):  
Xiaoxia Zhang ◽  
Zumin Xing ◽  
Jiyuan Li ◽  
Shuyi Tang ◽  
Yiwen Zhang

The aim of this study was to explore the neurocognitive effects of dexmedetomidine-loaded gold nanoparticles (AuNPs-dexmedetomidine) on anesthetized rats. Sixty Sprague Dawley rats (age, 2–3 weeks; weight, 250–280 g) were randomly divided into three groups (n = 20): the control group and two groups that received intraperitoneal injection of AuNPs-dexmedetomidine at 50 and 100 μg/kg each. Western blotting and RT-PCR were used to determine the protein and mRNA expression of GSK-3β, respectively. Compared with that in the control group, GSK-3β expression in AuNP-dexmedetomidine groups increased (P < 0.05). The protein expression of GSK-3β was higher and mRNA expression was significantly lower in the 100 μg/kg AuNP-dexmedetomidine group (P < 0.05). AuNPs-dexmedetomidine reduced the neurocognitive effect on anesthetized rats through the regulation of the GSK-3β signaling pathway.


1997 ◽  
Vol 272 (3) ◽  
pp. R1007-R1011 ◽  
Author(s):  
M. D. Barrachina ◽  
V. Martinez ◽  
J. Y. Wei ◽  
Y. Tache

Chronic treatment with leptin regulates body weight and energy balance and reduces food intake in obese and lean mice. In 18- to 20-h fasted lean mice (C57BL/6, +/+), we examined the acute effect of a single intraperitoneal injection of recombinant mouse leptin (0.12 mg/kg) on food intake and gastric emptying. Leptin reduced food intake, with a peak inhibition at the 5th h postinjection (69 +/- 12%/h), although there was no change in food consumption at the 1st h. Leptin did not alter the 4-h rate of gastric emptying of a solid nutrient meal (free access to Purina chow for either 1-, 2-, or 4-h period). In normal Sprague-Dawley rats fasted for 18-20 h, a single intraperitoneal injection of recombinant mouse leptin (0.2 or 1.2 mg/kg) did not modify the 7-h cumulative or hourly food intake. These results show that a single intraperitoneal injection of recombinant mouse leptin reduces food intake within 5 h while not influencing gastric emptying of ingested food in lean mice. Sprague-Dawley rats are unresponsive to the food intake-reducing effect of a single intraperitoneal injection of mouse leptin at a dose 10-fold higher than that shown to be effective in mice within the first 4-7 h postinjection.


1999 ◽  
Vol 277 (1) ◽  
pp. R301-R305 ◽  
Author(s):  
Sandra Boutellier ◽  
Thomas A. Lutz ◽  
Matthias Volkert ◽  
Erwin Scharrer

In former work, intraperitoneal injection of 2-mercaptoacetate (MA), an inhibitor of fatty acid oxidation, increased food intake in rats, which was attenuated by hepatic branch vagotomy, and intraportal injection of MA increased the discharge rate in hepatic vagal afferents. In the present study, we investigated, whether intraperitoneal injection or intraportal infusion of MA affects the hepatic membrane potential in rats in vivo. The liver cell membrane potential was measured in anesthetized Sprague-Dawley rats with the microelectrode technique. Intraperitoneal injection of MA at a dose of 800 μmol/kg body wt significantly decreased the hepatocyte membrane potential by 3.8 mV, whereas at a dose of 400 μmol/kg, the depolarization (1.5 mV) of the membrane was not significant. In another strain of Sprague-Dawley rats, however, MA (400 μmol/kg) produced a significant depolarization of the hepatocyte membrane 50 min (2.6 mV) and 2 h (2.9 mV) after intraperitoneal injection. Intraportal infusion of MA (400 μmol/kg) significantly depolarized the membrane 20 and 50 min after infusion by 3.3 and 4.1 mV, respectively. MA at a dose of 800 μmol/kg also depolarized the membrane (4.8 mV after 50 min). These findings in principle are consistent with the “potentiostatic” hypothesis, postulating a link between the hepatic membrane potential, afferent vagal activity, and the control of food intake.


2001 ◽  
Vol 35 (4) ◽  
pp. 307-314 ◽  
Author(s):  
E. Bamberg ◽  
R. Palme ◽  
J. G. Meingassner

Stress enhances the production of corticosteroids by the adrenal cortex, resulting in the increased excretion of their metabolites in urine and faeces. An intraperitoneal injection of radioactive corticosterone was applied to adult, male Sprague-Dawley rats to monitor the route and delay of excreted metabolites in urine and faeces. Peak concentrations appeared in urine after 3.2 ± 1.9 h and in faeces after 16.7 ± 4.3 h. Altogether about 20% of the recovered metabolites were found in urine and about 80% in faeces. Using high-performance liquid chromatography (HPLC), several peaks of radioactive metabolites were found. Some metabolites were detected by enzyme immunoassay (EIA) using two different antibodies (corticosterone, 11β-OH-aetiocholanolone). There was a marked diurnal variation with low levels of faecal corticosterone metabolites in the evening and higher values in the morning. This diurnal variation was influenced neither by the intraperitoneal injection of isotonic saline nor by ACTH. However, the administration of dexamethasone eliminated the morning peak for 2 days.


2004 ◽  
Vol 181 (2) ◽  
pp. 339-345 ◽  
Author(s):  
BM Cheung ◽  
IS Hwang ◽  
CY Li ◽  
WS O ◽  
KW Tsang ◽  
...  

Adrenomedullin (AM) is a peptide involved in cardiovascular homeostasis and in inflammation. We examined its expression in a rat model of endotoxaemia. Male Sprague-Dawley rats received intraperitoneal injection of 5 or 10 mg/kg lipopolysaccharide (LPS), or saline as control. Rats were killed at 1, 3, 6, 12 and 24 h after injection. LPS at 5 mg/kg, but not saline, increased plasma AM significantly at 3 h. At 10 mg/kg, plasma AM was raised at 3, 6 and 12 h. Immunoreactive AM concentration in lung increased after 5 or 10 mg/kg LPS, but not saline. PreproAM mRNA level in lung was significantly increased at 3 and 6 h. In conclusion, endotoxin stimulates the expression of AM in the lungs and increases its circulatory concentration. AM may be involved in the systemic response to sepsis.


PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0243108
Author(s):  
Yafang Li ◽  
Yiqiang Qiao ◽  
Huanhuan Wang ◽  
Zao Wang

In recent years, many studies have found that mechanical tension can activiate NF-kB signal pathway and NF-kB plays an important role in the process of osteogenesis. However, it is still unclear whether this process exists in the anterior palatal suture expansion. In this paper, we mainly studied the effect of intraperitoneal injection of PDTC on the NF-kB signaling pathway and osteogenesis index of the anterior palatal suture expansion model in young adult rats. The expansion model is grouped and established: 45 male 8-week-old Sprague-Dawley rats were randomly divided into three groups, an expansion only (EO) group, an expansion plus PDTC (PE) group, and a control group. The results revealed that PDTC inhibited the activity of NF-kB signaling pathway and promote one morphogenetic protein 2 (BMP-2), steocalatin (OCN) expression. Compared with the control group, the optical density (OD) value of BMP in the EO group and PE group rats increased significantly from the first day to the seventh day, and the difference was statistically significant (P<0.05). After 6.0Gy irradiation, PDTC administration group could slightly increase the total SOD level in the liver and serum of rats, and reduce the MDA level in the liver and serum, especially the effect of 60mg/kg and 90mg/kg was the most obvious.


2020 ◽  
Vol 53 (03) ◽  
pp. 357-362
Author(s):  
Dimpy Sharma ◽  
Subramania Iyer ◽  
Sobha Subramaniam ◽  
Janarthanan Ramu ◽  
Mohit Sharma ◽  
...  

Abstract Background Tracheal transplantation seems to be the logical step in the process of reconstruction of the trachea following a long-segment resection, which is usually done to treat malignant disease or benign stenosis of the airway caused by a traumatic, congenital, inflammatory, or iatrogenic lesion. Immunosuppression following transplant is essential but not ideal after oncoresection. Methods The tracheal allografts, harvested from Sprague Dawley rats, were implanted in the Wistar strain rat. The harvested tracheal grafts were divided into groups and subgroups, based on the layers of trachea, method of decellularization, and immunosuppression. The antigenicity of different layers of trachea and the effect of various decellularization methods were studied within three time frames, that is, day 3, 9, and 15. Result On structural analysis, the day 3 and day 15 samples showed no meaningful comparison could be made, due to extensive neutrophil infiltration in all three layers. The day 9 tracheal grafts showed loss of epithelium, with no signs of regeneration in most of the allografts. The subepithelial lymphoid infiltration was found to be severe in nonimmunosuppressed allografts. The group in which both inner and outer layers were removed showed moderate-to-severe infiltrate of lymphoid cells in all the allografts, but there was no cartilage loss, irrespective of the method of decellularization. The irradiated specimens retained the cartilage but showed extensive ischemic damage. Conclusion Rat trachea is a good model for tracheal transplant research but not adequately sturdy to sustain mechanical debridement. Irradiation and chemical decellularization eliminates the immune response but causes intense ischemic damage. Out of the three time frames, day 9 seemed to be the best to study the immune response. To substantiate the results obtained in this study, the immunohistochemical study of the allografts is needed to be performed among a larger group of animals.


1996 ◽  
Vol 271 (6) ◽  
pp. R1638-R1642 ◽  
Author(s):  
M. Monda ◽  
A. Sullo ◽  
E. De Luca ◽  
M. P. Pellicano

These experiments test the effect of intraperitoneal injection of lysine acetylsalicylate on 1) food intake and 2) the sympathetic and thermogenic changes induced by lesion of the lateral hypothalamus (LH). Food intake, firing rate of the nerves innervating interscapular brown adipose tissue (IBAT), and IBAT and colonic temperatures (TIBAT and TC) were monitored in male Sprague-Dawley rats lesioned in the LH. These variables were measured before and after intraperitoneal injection of lysine acetylsalicylate. The same variables were also monitored in 1) lesioned rats with intraperitoneal administration of saline, 2) sham-lesioned animals with intraperitoneal injection of lysine acetylsalicylate, and 3) sham-lesioned rats with intraperitoneal injection of saline. The results show that lysine acetylsalicylate modifies the aphagia by increasing food intake and also reduces the enhancements in firing rate, TIBAT, and TC induced by LH lesion. These findings suggest that prostaglandin synthesis plays a key role in the control of eating behavior in LH-lesioned rats by acting on the sympathetic and thermogenic changes induced by LH lesion.


1985 ◽  
Vol 249 (3) ◽  
pp. G321-G327 ◽  
Author(s):  
L. E. Benjamin ◽  
R. D. Steele

The effect of portacaval shunt (PCS) on methionine metabolism in the rat was investigated. Male Sprague-Dawley rats were subjected to PCS and maintained on an 18% casein diet. Growth curves of operated rats were similar to controls. PCS rats excreted more urinary 35SO4 and less [35S]taurine than controls after intraperitoneal injection of 0.3 mmol/100 g [35S]methionine or [35S]cysteine. Total urinary taurine excretion was similar in PCS and control rats after a methionine or cysteine load; however, under basal conditions PCS rats had higher urinary taurine levels than controls, indicating that PCS may cause the taurine pool to be expanded. Hepatic methionine, S-adenosylmethionine, and cysteine pools were significantly decreased in PCS rats, while S-adenosylhomocysteine levels were unchanged. Relative rates of transsulfuration in PCS and control rats were studied by following the decrease in the 3H-to-35S ratio in liver protein after injection of [methyl-3H]methionine and [35S]methionine, and no difference in flux of 35S from [35S]methionine to [35S]cysteine was found. Similarly, total hepatic activities of methionine adenosyltransferase, cystathionine synthase, and cystathionine gamma-lyase were unchanged in PCS rats. These results indicate that altered methionine metabolism in PCS rats is not explained by changes in conversion of methionine to cysteine via the transsulfuration pathway.


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