摘要:

Excessive alcohol consumption represents a major human health threat. The frequency and severity of infections in alcoholics is often pronounced, suggesting impaired immune function in these patients. The precise effect of ethanol on cells of the immune system is poorly understood. We have previously shown that synthetic copolymers of L‐amino acids, GT and GAT, are powerful tools for clarifying the role of regulatory T‐cells in both cell‐mediated and humoral immunity in inbred mouse strains. We asked whether these same antigens would have application to a murine model of ethanol consumption. In this study, female mice were placed on a nutritionally complete liquid diet containing 35% ethanol‐derived calories. As control, mice either were placed on a liquid control diet that isocalorically substitutes sucrose for ethanol or remained on a solid diet consisting of standard laboratory chow and water ad libitum. Our data show that the liquid ethanol diet severely inhibits two measures of cell‐mediated immunity, the ability of responder B6 mice to make an anti‐GAT delayed hypersensitivity and GAT‐specific T‐cell proliferative responses as compared with pair‐fed liquid control diet or solid diet controls. On the contrary, this liquid ethanol diet does not significantly impair humoral immunity; it allows nonresponder C57BL/6 or C3H/HeN mice to respond in vivo to GT immunization. These findings suggested to us that the effect of ethanol may occur prior to antigenic stimulation, and this was confirmed by in v

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1994.tb00872.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Modification of the mucosa‐associated intestinal immune system of female C57BL/6 mice was studied during consumption of the Lieber‐DeCarli diet supplemented with 5% v/v ethanol or laboratory chow with ethanol (20% w/v) in the drinking water. All groups received ethanol for 11 weeks. Mice fed the Lieber‐DeCarli diet had fewer CD8+cells/villus than the chow‐fed controls. Mice that received ethanol in the drinking water had fewer IgA‐containing cells and CDB+cells than controls. There were no differences in the number of cells in the mesenteric lymph nodes between ethanol‐treated mice and their respective controls. Nevertheless, chow‐fed control mice had more cells than those fed the Lieber‐DeCarli control diet. Although no differences were detected in the percentages of CD4+, CD8+, LECAM‐1+, and LECAM‐1+CD4+cells, there was a decrease in the percentage of LECAM‐1+CD8+cells in ethanol‐fed mice when compared with their Lieber‐DeCarli controls. Mice receiving ethanol in the drinking water showed alterations in the CD4 CD45RC subsets and in the CD8 CD45RC subsets. Similar results were observed in mice receiving Lieber‐DeCarli diets alone or supplemented with ethanol. The low dose, chronic exposure of dietary ethanol in the Lieber‐DeCarli‐fed mice did not significantly affect the numbers of various thymocyte subsets. But, a decrease in the percentage of CD4‐CD8+cells was observed in the thymus of mice receiving ethanol in the drinking water. Chronic ethanol consumption caused significant decreases in the number of CD8+and IgA+cells in the intestinal lamina propria, imp

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1994.tb00873.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Alcoholic patients often have impaired immune function, yet little is known about the precise mechanism(s) of this impairment. We have previously shown that ethanol consumption by mice alters copolymer‐specific humoral and cellular immune responses. In this study, we asked whether alcohol consumption by mice would phenotypically alter lymphocyte populations. Female C57BL/6 mice were fed a nutritionally complete liquid diet containing 35% ethanol‐derived calories for up to 8 days. As controls, mice either were fed a liquid control diet that isocalorically substitutes sucrose for ethanol or remained on a standard solid diet and water ad libitum. Although mice fed ethanol‐containing liquid or pair‐fed control liquid diets have decreased numbers of spleen cells compared with solid diet controls, only the ethanol‐containing diet allowed normally nonresponder C57BL/6 spleen cells to make antibody responses to the poly(Glu50Tyr50) synthetic copolymer antigen. Flow cytometric analysis of splenic lymphocyte populations of mice on the ethanol‐containing diet shows an increase in the relative proportion of T‐lymphocytes as compared with mice on either solid or liquid control diets. No such change is seen for either B‐cell or natural killer cell populations in these same mice. Both liquid control and liquid ethanol diets caused a slight decrease in the CD4:CD8 ratios of splenic T‐lymphocytes. We see the relative percentage of T‐cells bearing theαβ‐cell receptor (TcR) increases in the spleens of liquid ethanol diet mice; a smaller increase TcRαβusage is seen in the spleens of liquid control mice, compared with solid diet mice. Flow cytometric analysis shows that little, if any, difference exists in TcRγδexpression between the liquid ethanol and either the liquid control or solid diet groups. Preliminary analysis of TcRαβsubsets suggest that ethanol increases the percentage of T‐cells expressing Vβ5 and Vβ8, and decreases the percentage of Vβ11 expressing cells. These findings suggest that, in addition to modifying the immune response, ethanol alters the phenotypi

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1994.tb00874.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Ethanol is a recognized immunosuppressive agent in the chronic alcoholic. However, the effects of ethanol exposure on the developing immune system have not been extensively investigated. This study evaluated the effects of early postnatal ethanol exposure, via breast milk, on splenic lymphocyte differentiation antigen expression in offspring reared by ethanol‐fed mice. Maternal mice were fed a liquid diet containing 20% ethanol‐derived calories during pregnancy (E‐P), pregnancy and lactation (E‐PL), or lactation (E‐L). Ad libitumfed (C) and pair‐fed (PF) control groups, fed a control liquid diet, were included. Expression of differentiation antigens on splenic lymphocytes from 21‐day‐old offspring reared by females in 1 of the 3 ethanol exposure conditions was evaluated by flow cytometry. Offspring reared by E‐P females had similar numbers of splenic lymphocytes as offspring reared by C and pair‐fed during pregnancy (PF‐P) females. In contrast, offspring reared by E‐PL and E‐L females had fewer splenic lymphocytes than both PF‐PL and PF‐L (respectively), and C offspring. The number of Thy 1.2+, CD4+, CD8+, and IgG+(B‐cell) splenic lymphocytes was reduced in E‐PL and E‐L offspring compared with PF and C offspring. E‐P offspring had fewer CD4+and IgG+splenic lymphocytes than C, but not PF‐P, offspring. The percentage of Thy 1.2+splenic lymphocytes was significantly reduced among E‐PL and E‐L offspring compared with PF‐PL and PF‐L (respectively), and C offspring. These results suggest that ethanol exposure of female mice during pregnancy, pregnancy and lactation, or lactation alone, alters the phenotypic development of splenic lymphocytes of offspring reared by these females. The greatest effect on differentiation antigen expression occurred when females consumed ethanol during the period of lactation. We speculate that direct exposure of the nursing offspring to ethanol via the breast milk was responsible for the reductions in specific splenic lymphocyte populations. These data demonstrate that mice reared by females fed ethanol during the early postnatal period have a marked depletion of each of the major subpopulations of splenic lymphocytes, and that Thy 1.2+lymp

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1994.tb00875.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The effects of alcohol on blastocyst implantation and fecundity were determined. Pregnant rats (insemination = day 1) received vehicle only (water), or alcohol (2 or 4 g/kg body weight) daily by feeding tube on days 1–4 and the time of implantation determined on day 5 or fecundity assessed on day 19. Implantation sites were rendered visible by the blue‐reaction; fecundity was expressed as the ratio of live fetuses to total implantations. The time course of blastocyst implantation was advanced by alcohol (2 g/kg dose). At 1000 hr, 1.9 vs. 0.9 blastocysts had implanted in treated vs. controls. By 1200 hr, 66 vs. 17% of blastocysts had implanted and by 1500 hr 90 vs. 52% had implanted in the 2 g/kg dose group vs. controls. Blastocyst implantation was not consistently advanced by the 4 g/kg dose of alcohol. The total number of blastocysts ultimately implanting did not differ between groups (control: 7:0 ± 0.9; 2 g:7.3 ± 0.9; 4 g:7.1 ± 0.5 sites/cornu at 1800 hr). Fecundity did not differ markedly between control and the 2 g/kg dose group (97 vs. 96%, respectively), but was reduced in the 4 g/kg dose group (58%). The results indicate that daily administration of alcohol (2 g/kg body weight) during the preimplantation period (days 1–4) advances the time course of blastocyst implantation without reducing f

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1994.tb00876.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

This study examines the effect of ethanol (ETOH) exposure and nutrient restriction on the release of insulin‐like growth factor (IGF)‐II from 18‐ and 20‐day explanted fetal organs. Fetuses were exposed to ETOH (E) in utero by feeding dams a 36% (calories derived from ETOH: 6.6% v/v) ETOH liquid diet. Control fetuses were offsprings of dams either pair‐fed (P) a control liquid diet or ad libitum (A) fed a standard pelleted lab chow. Brain, heart, kidney, liver, lung, muscle, and placenta of fetuses from the same litter were pooled and explanted, and IGF‐II concentration in explanted media was analyzed by radioimmunoassay. Maternal and fetal weights were determined during pregnancy and at sacrifice, respectively, to evaluate the influence of ETOH on growth.Both maternal and fetal weights were substantially reduced by ETOH on 18 and 20 days of gestation compared with both A and P controls. At 18 days of gestation, E fetuses (1.33 ± 0.03 g) weighed less than either A (1.47 ± 0.03 g) or P (1.54 ± 0.04 g) fetuses. By 20 days, A mean fetal weight (4.19 ± 0.23 g) was significantly greater than both P (3.74 ± 0.06 g) and E (3.28 ± 0.06 g) fetuses. IGF‐II concentration in media from 18‐day fetal explants was highest from E (brain, heart, liver, and placenta) and P tissues (kidney, lung, and muscle). IGF‐II in media from A tissues (except placenta) was lower than both E and P levels. A significant difference between treatments occurred in heart. By 20 days, IGF‐II levels were highest in media from all A tissues (except placenta). IGF‐II in media from E tissues (except lung) was lower than those from P tissues. A significant difference between treatments occurred in the brain.With regard to the developmental pattern, IGF‐II release generally increased between 18 and 20 days of gestation, with the greatest increases occurring in A tissues. Increased secretion by P tissues was greater than that by corresponding E tissues, and tended to follow the A trend. On the other hand, E brain, kidney, and placenta released only slightly more IGF‐II at 20 days compared to 18 days, whereas E heart, liver, lung, and muscle released slightly less hormone.This study suggests that even moderate nutrient deprivation influences the pattern of IGF‐II release from fetal organs, even though there is only a small decrease in overall body size. At the same level of nutrient deprivation, ETOH more dramatically alters both fetal weight and the pattern of IGF‐II release. Because IGFs are autocrine/ paracrine factors that influence growth, differentiation, and function, the reduced availability of IGF‐II may be one of the factors contributing to ETOH‐induced growth retardation and impaired fu

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1994.tb00877.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

COLD and HOT mice have been selected to be sensitive or resistant, respectively, to the acute hypothermic effect of ethanol. Previous studies have found HOT mice to be relatively resistant to the development of tolerance to this effect, whereas COLD mice readily develop tolerance. By administering several doses of ethanol and recording multiple postdrug temperatures, in the current study we equated the selected lines for area under the curve describing initial hypothermic response over time, a measure reflecting both maximal hypothermia achieved and the duration of total hypothermic response. The dose‐response function for COLD mice was much steeper than that for HOT mice, and HOT mice recovered to baseline body temperatures more slowly. Doses were administered daily for 5 days. Both lines developed tolerance to ethanol hypothermia. The magnitude of tolerance developed was greater in COLD than in HOT mice. At higher doses, HOT mice showed a progressively enhanced hypothermic response over days (i.e., sensitization

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1994.tb00878.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Previous work in this and other laboratories has demonstrated that in utero ethanol exposure adversely affects the development of the serotonergic, dopaminergic, cholinergic, and other neurotransmitter systems. In several of these systems, receptor number is significantly altered. To determine whether the altered number of two G protein‐linked receptors is reflected in changes in cell function, we examined dopamine‐stimulated adenylate cyclase in the striatum and cortex and carbachol‐stimulated phosphoinositide (PI) hydrolysis in the cortex. Serotonin‐stimulated cortical PI hydrolysis was assessed for comparison. We also studied G proteins that link adenylate cyclase and other second messenger systems to their receptors. The G proteins that were analyzed include the α‐subunits for Ga, Go, G11, G12, and G13. G proteins were analyzed in the cortex and cortical regions, as well as in the brain stem.The results of these experiments demonstrated that dopaminestimulated adenylate cyclase activity was comparable in the striatum of 5‐ and 19‐day offspring of control and ethanol‐fed rats and in the motor cortex of 19‐day offspring. We also found that carbachol‐ and serotonin‐stimulated hydrolysis of cortical phosphoinositides was unchanged in ethanol‐exposed offspring on gestational day 19, and on postnatal days 5 and 19. G protein content was examined by Western blot analysis, using antibodies directed against the α‐subunits of Ga, Go, and the G11/G12and G13/Gocombinations. These investigations indicated that, with two minor exceptions (∼10% change in the proteins detected by antibodies against the α‐subunits of the G11/G12and G13/Gocombinations), there were no significant differences in the content o

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1994.tb00879.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Fluorescent probes located in different membrane regions were used to evaluate effects of ethanol (50 and 100 mM) on structural parameters (protein distribution, fluidity of total and annular lipid, and thickness of the bilayer) of synaptic plasma membranes (SPMs) from brain cortex of High‐Alcohol Sensitivity (HAS) and Low‐Alcohol Sensitivity (LAS) rats. An experimental procedure based on radiationless energy transfer from tryptophan of membrane proteins to pyrene, 1,3‐bis‐(1‐pyrene)propane(pyr‐C3‐pyr), or 1,6‐diphenyl‐1,3,5‐hexatriene (DPH), as well as pyr‐C3‐pyr monomer‐eximer formation and DPH polarization, and energy transfer from pyrene monomers to 1‐anilinonaphthalene‐8‐sulfonic acid (ANSA) was utilized. The efficiency of energy transfer from tryptophan to pyrene was sensitive to protein clustering induced in SPMs by concanavalin A. Efficiency of energy transfer from pyrene monomers to ANSA was different for vesicles of dimyristoyl phosphatidyl choline, dipalmitoyl phosphatidyl choline, and distearoyl phosphatidyl choline, consistent with differences in the thickness of these lipid bilayers. Without ethanol, there were no significant differences between the structural parameters of SPMs from HAS and from LAS rats. Addition of ethanol (50 mM) changed protein distribution (increased clustering) only in membranes from HAS rats and had no effect on the structure of membranes from LAS rats. A larger concentration of ethanol (100 mM) changed the fluidity of annular and total lipid in both lines of rats, but changed protein distribution and decreased thickness of the membranes from HAS rats with no effect on these parameters in SPMs from LAS animals. Ethanol (50 and 100 mM) decreased the binding affinity of ANSA for membranes from HAS, but not LAS rats. Genetic differences in ethanol sensitivity of HAS and LAS rats may be related to effects of ethanol on protein mobility, protein‐protein interactions, or membrane thickness, but do not appear to be due to effects of ethanol o

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1994.tb00880.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Methysergide (MS), a postsynaptic serotonin antagonist, was administered acutely in three experiments in relation to water or 5% ethanol solution intake of 24‐hr, water‐deprived male Sprague‐Dawley rats. In the first experiment, MS significantly increased the consumption of ethanol at doses of 0.25, 2.0, and 4.0 mg/kg. Water intake was significantly increased by MS at the 2.0 mg/kg dose. In the second experiment, which was different from the first one in that MS was administered during the dark cycle, ethanol solution intake was again significantly increased at all three levels. In the third experiment, fenfluramine (FFL) and fluoxetine (FLU) were administered acutely (at 8 mg/kg) after MS (0.25 mg/kg) followed by measuring water or ethanol solution intake. FFL and FLU significantly decreased intake of both water and ethanol solution, a process that was significantly reversed by MS; to a greater degree for FLU (74%) than for FFL (57%). The successful use of MS in increasing ethanol intake in these studies may be due to the low doses used in comparison with earlier unsuccessful attempts. The procedure of treating 24‐hr, water‐deprived rats with acute doses of pre‐ and postsynaptic serotonin agonists and antagonists appears to be a useful model for further elucidation of their interaction in ethanol consummato

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1994.tb00881.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY