Intracellular signal systems in the epithelium- and endothelium-dependent relaxation of smooth muscles

The research of mechanisms of a regulation electrical and contractile of properties of unstriated muscles of an internals remains by an actual problem of modern physiology and medicine. Already now it is possible to state that the efficacy of means of correction of distresses of an internals depends on a degree of a level of scrutiny of these mechanisms. Among physiologically active substances effecting on smooth muscle cells (SM), the special relaxing factor synthesized by endotheliocytes, epithelial cells and SM. Identified by the majority of the explorers as oxide of nitrogen (NO), relaxing factor responds for exhibiting of many myogenic responses of pots and pneumatic routes. The mechanisms of synthesis and implementation of effects of this factor in SM cells up to the extremity are not clarified. The considerable advance in learning mechanisms of operation relaxing factor on SM is connected to discovering of ability of some nitro compounds to replicate NO-dependent relaxing effects in these cells. The main systems of intracellular regulation are involved in mechanisms of implementation endothelial and epithelial local regulatory effects on SM. The majority of the explorers bind an epithelium-dependent release phenomenon SM to an activation of a solvable fraction guanilatcyclase, found in the majority of cells, and effects of cGMP-dependent protein kinases. There are reports on ability of inhibitors NO-sintase to depress a release phenomenon SM of pots and bronchuses, about dependence of a mechanical strain SM of pots and respiratory tract from a contents cGMP in cells. However there are datas giving establishments to guess, that alongside with guanilatciclase in a release phenomenon SM, induced relaxing factors or nitro compounds, the immediate involvement is accepted by cAMP-dependent protein kinases. The most probable point of interaction cAMP and cGMP-dependent processes is phospodiesterase of cyclic nucleotides. It citosolium the enzyme labilized by calmodulin, is capable to carry out a hydrolysis of both cyclic nucleotides, and the affinity native phospodiesterase to cGMP exceeds affinity to cAMP more, than on the order. It is impossible to eliminate immediate interference of NO-dependent processes in a regulation of activity contractile proteins. The ability cGMP-dependent processes to depressing mechanisms of phosphorylation and intensifying of a dephosphorylization of contraktion proteins SM is shown. At these processes can variate and affinity of the acto-miosin complex to ions of calcium, producing a release phenomenon of smooth muscles. On all visibility, production relaxing of the factor and the implementation is epithelial and endothelium-SM of mutual relation in a respiratory tract and pots comes true by modulating influence at the calcium signal system of other systems. For example, production relaxing of the factor by an epithelium and endothelium, being calcium-dependent process, is regulated at involvement calmodulin-similar Ca(2+)-connecting proteins and protein kinase C. Control of tone SM through change of membrane potential relaxing factor carries out by paravariation of potassium conduction of a membrane SM, and, is more probable than all through calcium-dependent and ATP-sensitive components. Potencial-dependent control of a muscle tone comes true through change of efficacy of an operation from a branch of the calcium signal system and calcium pompes at submaximal concentrations of free calcium in citosolium.     

Scaffolds for engineering smooth muscle under cyclic mechanical strain conditions

Cyclic mechanical strain has been demonstrated to enhance the development and function of engineered smooth muscle (SM) tissues, but appropriate scaffolds for engineering tissues under conditions of cyclic strain are currently lacking. These scaffolds must display elastic behavior, and be capable of inducing an appropriate smooth muscle cell (SMC) phenotype in response to mechanical signals. In this study, we have characterized several scaffold types commonly utilized in tissue engineering applications in order to select scaffolds that exhibit elastic properties under appropriate cyclic strain conditions. The ability of the scaffolds to promote an appropriate SMC phenotype in engineered SM tissues under cyclic strain conditions was subsequently analyzed. Poly(L-lactic acid)-bonded polyglycolide fiber-based scaffolds and type I collagen sponges exhibited partially elastic mechanical properties under cyclic strain conditions, although the synthetic polymer scaffolds demonstrated significant permanent deformation after extended times of cyclic strain application. SM tissues engineered with type I collagen sponges subjected to cyclic strain were found to contain more elastin than control tissues, and the SMCs in these tissues exhibited a contractile phenotype. In contrast, SMCs in control tissues exhibited a structure more consistent with the nondifferentiated, synthetic phenotype. These studies indicate the appropriate choice of a scaffold for engineering tissues in a mechanically dynamic environment is dependent on the time frame of the mechanical stimulation, and elastic scaffolds allow for mechanically directed control of cell phenotype in engineered tissues.     

Gliding Motility Mutants of Myxococcus xanthus

Two gliding motility mutants of Myxococcus xanthus are described. The semimotile mutant (SM) originated by high-frequency segregation from the motile FB(t) strain. Segregation was enhanced by acridine dye treatment. SM cells glide only when apposed to other cells in a swarm. The nonmotile strain (NM) originated by mutation from SM. NM cells neither glide individually nor cooperatively. FB(t), SM, and NM are indistinguishable with respect to fine structure, vegetative growth rate, glycerol-induced microcyst formation, spheroplasting, bacteriophage sensitivity, and responses to light. The motility mutants are more resistant to penicillin and more sensitive to actinomycin D than is the gliding wild type. The NM mutant is also a morphogenetic mutant; it is unable to form fruiting bodies.     

Physiologic effects of forced down-regulation of dnaK and groEL expression in Streptococcus mutans

Strains of Streptococcus mutans lacking DnaK or GroEL appear not to be isolable. To better distinguish the roles played by these chaperones/chaperonins in the physiology of S. mutans, we created a knockdown strategy to lower the levels of DnaK by over 95% in strain SM12 and the level of GroEL about 80% in strain SM13. Interestingly, GroEL levels were approximately twofold higher in SM12 than in the parent strain, but the levels of DnaK were not altered in the GroEL knockdown strain. Both SM12 and SM13 grew slower than the parent strain, had a strong tendency to aggregate in broth culture, and showed major changes in their proteomes. Compared with the wild-type strain, SM12 and SM13 had impaired biofilm-forming capacities when grown in the presence of glucose. The SM12 strain was impaired in its capacity to grow at 44 degrees C or at pH 5.0 and was more susceptible to H(2)O(2), whereas SM13 behaved like the wild-type strain under these conditions. Phenotypical reversions were noted for both mutants when cells were grown in continuous culture at a low pH, suggesting the occurrence of compensatory mutations. These results demonstrate that DnaK and GroEL differentially affect the expression of key virulence traits, including biofilm formation and acid tolerance, and support that these chaperones have evolved to accommodate unique roles in the context of this organism and its niche.     

Tissue mechanical behavior of tendinous fibers under statistical and dynamic requirements

With a device for dynamical processes tension tests were performed on bundles of collagen fibres of human and bovin origin. Part of the studies were performed under statical condition with an universal materials testing machine, equipped with a closed loop feed back control system. If the force is to be kept constant subsequently to a strain process on a collagen fiber bundle (isotonic condition), the fiber length must increase (creep phenomenon, retardation). The force decreases under constant length after a preceding strain process (relaxation). In analogy to the statical relaxation, statical isorheological line, and statical force recovery curve the dynamical (cyclic) relaxation, dynamical (cyclic) isorheological curve, and dynamical (cyclic) force recovery curve are described. The mechanical-rheological properties collagen fiber bundles are discussed in relation to functional anatomy.     

Positive force feedback in bouncing gaits?

During bouncing gaits (running, hopping, trotting), passive compliant structures (e.g. tendons, ligaments) store and release part of the stride energy. Here, active muscles must provide the required force to withstand the developing tendon strain and to compensate for the inevitable energy losses. This requires an appropriate control of muscle activation. In this study, for hopping, the potential involvement of afferent information from muscle receptors (muscle spindles, Golgi tendon organs) is investigated using a two-segment leg model with one extensor muscle. It is found that: (i) positive feedbacks of muscle-fibre length and muscle force can result in periodic bouncing; (ii) positive force feedback (F+) stabilizes bouncing patterns within a large range of stride energies (maximum hopping height of 16.3 cm, almost twofold higher than the length feedback); and (iii) when employing this reflex scheme, for moderate hopping heights (up to 8.8 cm), an overall elastic leg behaviour is predicted (hopping frequency of 1.4-3 Hz, leg stiffness of 9-27 kN m(-1)). Furthermore, F+ could stabilize running. It is suggested that, during the stance phase of bouncing tasks, the reflex-generated motor control based on feedbacks might be an efficient and reliable alternative to central motor commands.     

Cross-resistance ofEscherichia coli B/r tocis-platinum (II) diamminochloride,UV light and alkylating agents

Gradual transfers of the strain Escherichia coli B/r on M9 agar with increasing concentrations of cis-platinum (II) diamminochloride (cis-Pt(II)) yielded a resistant strain SM 405 capable of growing on liquid M9 medium containing 250 muM cis-Pt(II). The parent strain Escherichia coli B/r is completely inhibited in both division and growth at cis-Pt(II) concentrations as low as 30 muM. The resistant mutant has a longer doubling time than the parent strain. No other differences were found between the two strains. To elucidate the nature of the resistance, the effect of cis-Pt(II) on the survival of the two strains was compared with that of nitrogen mustard, UV light and ethyl methanesulphonate (EMS). The resistant strain SM 405 was found to be more hardened against the lethal action of UV light and nitrogen mustard but less so against EMS. It had also a higher ability of a host-cell reactivation of UV-irradiated phage T3. The different resistance of the B/r and SM 405 strains is probably due to a mutation increasing the effectiveness of the excision repair in the latter.     

Genetic loci that regulate healing and regeneration in LG/J and SM/J mice

MRL mice display unusual healing properties. When MRL ear pinnae are hole punched, the holes close completely without scarring, with regrowth of cartilage and reappearance of both hair follicles and sebaceous glands. Studies using (MRL/lpr × C57BL/6)F₂ and backcross mice first showed that this phenomenon was genetically determined and that multiple loci contributed to this quantitative trait. The lpr mutation itself, however, was not one of them. In the present study we examined the genetic basis of healing in the Large (LG/J) mouse strain, a parent of the MRL mouse and a strain that shows the same healing phenotype. LG/J mice were crossed with Small (SM/J) mice and the F₂ population was scored for healing and their genotypes determined at more than 200 polymorphic markers. As we previously observed for MRL and (MRL × B6)F₂ mice, the wound-healing phenotype was sexually dimorphic, with female mice healing more quickly and more completely than male mice. We found quantitative trait loci (QTLs) on chromosomes (Chrs) 9, 10, 11, and 15. The heal QTLs on Chrs 11 and 15 were linked to differential healing primarily in male animals, whereas QTLs on Chrs 9 and 10 were not sexually dimorphic. A comparison of loci identified in previous crosses with those in the present report using LG/J × SM/J showed that loci on Chrs 9, 11, and 15 colocalized with those seen in previous MRL crosses, whereas the locus on Chr 10 was not seen before and is contributed by SM/J.     

Statistical Mechanics of the Human Placenta: A Stationary State of a Near-Equilibrium System in a Linear Regime

All near-equilibrium systems under linear regime evolve to stationary states in which there is constant entropy production rate. In an open chemical system that exchanges matter and energy with the exterior, we can identify both the energy and entropy flows associated with the exchange of matter and energy. This can be achieved by applying statistical mechanics (SM), which links the microscopic properties of a system to its bulk properties. In the case of contractile tissues such as human placenta, Huxley’s equations offer a phenomenological formalism for applying SM. SM was investigated in human placental stem villi (PSV) (n = 40). PSV were stimulated by means of KCl exposure (n = 20) and tetanic electrical stimulation (n = 20). This made it possible to determine statistical entropy (S), internal energy (E), affinity (A), thermodynamic force (A / T) (T: temperature), thermodynamic flow (v) and entropy production rate (A / T x v). We found that PSV operated near equilibrium, i.e., A ≺≺ 2500 J/mol and in a stationary linear regime, i.e., (A / T) varied linearly with v. As v was dramatically low, entropy production rate which quantified irreversibility of chemical processes appeared to be the lowest ever observed in any contractile system.     

Behaviour of a surface EMG based measure for motor control: Motor unit action potential rate in relation to force and muscle fatigue

Surface electromyography parameters such as root-mean-square value (RMS) and median power frequency (FMED) are commonly used to assess the input of the central nervous system (CNS) to a muscle. However, RMS and FMED are influenced not only by CNS input, but also by peripheral muscle properties. The number of motor unit action potentials (MUAPs) per second, or MUAP Rate (MR), being the sum of the firing rates of the active motor units, would reflect CNS input solely. This study explored MR behaviour in relation to force and during a fatiguing contraction in comparison to RMS and FMED.In the first experiment (n = 10) a step contraction of shoulder elevation force (20–100 N) was performed while multi-channel array EMG was recorded from the upper trapezius muscle. The sensitivity of MR for changes in force (1.8%/N) was almost twice as high as that of RMS (0.97%/N), indicating that MR may be more suitable for monitoring muscle force. The second experiment (n = 6) consisted of a 15-min isometric contraction of the biceps brachii. MR increased considerably less than RMS (0.9% vs. 4.1%), suggesting that MR selectively reflects central motor control whereas RMS also reflects peripheral changes. These results support that, at relatively low force levels, MR is a suitable parameter for non-invasive assessment of the input of the CNS to the muscle.     

An Escherichia coli mutant exhibiting temperature-sensitive ATP synthesis

A mutant strain SM434 (ttr-3) of Escherichia coli that exhibits a temperature-sensitive Unc(succinate-nonutilizing) phenotype was characterized. The mutant allele ttr-3 was not linked to the ilvA gene, but was complemented by Fill carrying 81 min-91 min of the E. coli chromosome. The mutant strain SM434 exhibited resistance to N,N'-dicyclohexylcarbodiimide (DCCD) and a temperature-sensitive phenotype at the level of ATP synthesis, compatible with that of cell growth. These findings indicate that the mutant strain SM434 could carry a mutation (ttr-3) in an unknown gene responsible for the energy-transduction system.     

Rotamer strain energy in protein helices - quantification of a major force opposing protein folding

It is widely believed that the dominant force opposing protein folding is the entropic cost of restricting internal rotations. The energetic changes from restricting side-chain torsional motion are more complex than simply a loss of conformational entropy, however. A second force opposing protein folding arises when a side-chain in the folded state is not in its lowest-energy rotamer, giving rotameric strain. chi strain energy results from a dihedral angle being shifted from the most stable conformation of a rotamer when a protein folds. We calculated the energy of a side-chain as a function of its dihedral angles in a poly(Ala) helix. Using these energy profiles, we quantify conformational entropy, rotameric strain energy and chi strain energy for all 17 amino acid residues with side-chains in alpha-helices. We can calculate these terms for any amino acid in a helix interior in a protein, as a function of its side-chain dihedral angles, and have implemented this algorithm on a web page. The mean change in rotameric strain energy on folding is 0.42 kcal mol-1 per residue and the mean chi strain energy is 0.64 kcal mol-1 per residue. Loss of conformational entropy opposes folding by a mean of 1.1 kcal mol-1 per residue, and the mean total force opposing restricting a side-chain into a helix is 2.2 kcal mol-1. Conformational entropy estimates alone therefore greatly underestimate the forces opposing protein folding. The introduction of strain when a protein folds should not be neglected when attempting to quantify the balance of forces affecting protein stability. Consideration of rotameric strain energy may help the use of rotamer libraries in protein design and rationalise the effects of mutations where side-chain conformations change.     

Phenotypic switching of Cryptococcus neoformans can influence the outcome of the human immune response

The human pathogenic fungus Cryptococcus neoformans exhibits the phenomenon of phenotypic switching, a process that generates variant colonies that can differ in morphology, virulence and other characteristics such as capsular glucuronoxylomannan (GXM) size and structure. A previous study established that mucoid colony (MC) variants of C. neoformans were more virulent and elicited a different inflammatory response than smooth colony (SM) variants. In this study, we investigated the interaction of cells from MC and SM variants and their respective GXMs with human T cells and monocytes. Specifically, we measured CD40, CD80 and CD86 expression, lymphoproliferation and interleukin (IL)-4, IL-10, interferon (IFN)-gamma and IL-12Rbeta2 expression in the presence and absence of variant cells and their GXMs. For some immune parameters, both MC and SM strains produced similar results, in particular no differences were observed in IL-4 induction. However, for other critical parameters, including CD86 expression, lymphoproliferation and IL-10 production, the MC variant had effects that can be expected to impair the immune response. Hence, a single C. neoformans strain can elicit several different immune responses depending on the colony type expressed, and this is unlikely to be accounted for by differences in phagocytosis only. The results provide a potential explanation for the higher virulence of the MC variant based on the concept that these cells inhibit the development of a vigorous immune response. Furthermore, the results suggest a mechanism by which phenotypic switching can generate variants able to evade the immune response.     

Effect of the cortex-lytic enzyme SleC from non-food-borne Clostridium perfringens on the germination properties of SleC-lacking spores of a food poisoning isolate

The hallmark of bacterial spore germination is peptidoglycan cortex hydrolysis by cortex-lytic enzymes. In spores of Clostridium perfringens wild-type strain SM101, which causes food poisoning, the sole essential cortex-lytic enzyme SleC is activated by a unique serine protease CspB. Interestingly, the non-food-borne wild-type strain F4969 encodes a significantly divergent SleC variant (SleCF4969) and 3 serine proteases (CspA, CspB, and CspC). Consequently, in this study we evaluated the functional compatibility of SleCF4969 and SleCSM101 by complementing the germination phenotypes of SM101ΔsleC spores with sleCF4969. Our results show that although pro-SleCF4969 was processed into mature SleCF4969 in the SM101ΔsleC spores, it partially restored spore germination with nutrient medium, with a mixture of ?-asparagine and KCl, or with a 1:1 chelate of Ca2+ and dipicolinic acid. While the amount of dipicolinic acid released was lower, the amount of hexosamine-containing material released during germination of SM101ΔsleC(sleCF4969) spores was similar to the amount released during germination of SM101 wild-type spores. The viability of SM101ΔsleC(sleCF4969) spores was 8- and 3-fold lower than that of SM101 and F4969 spores, respectively. Together, these data indicate that the peptidoglycan cortex hydrolysis machinery in the food poisoning isolate SM101 is functionally divergent than that in the non-food-borne isolate F4969.     

Effects of sex and estrogen on myosin COOH-terminal isoforms and contractility in rat aorta

We reported that estrogen treatment of ovariectomized rats increased uterine smooth muscle contractility and the ratio of the COOH-terminal myosin heavy chain isoform SM1 (204 kDa) and SM2 [200 kDa; Hewett TE, Martin AF, Paul RJ. J Physiol (Lond) 460: 351-364, 1993]. We extended this model to study sex and estrogen effects on vascular contractility. Experimental groups included 10- to 14-wk-old male (M), female (F), ovariectomized female (OF), and OF treated with estrogen (OF&E) for 7 days with a subcutaneous pellet delivery system, resulting in 17beta-estradiol of 85 (OF&E) vs. 5 (OF or M) pg/ml. The SM1-to-SM2 ratio increased from 1.8 to 2.6 in thoracic aorta, similar to uterine muscle. Isometric force was measured in 5-mm segments of intact and endothelium-denuded (-endo) aorta. With KCl, the maximum forces were in the order OF approximately M > OF&E, and ED50 OF&E > OF approximately M. Differences in ED50 with estrogen persisted after endothelial denudation. The decreased force in -endo OF aorta was not seen in OF&E, suggesting that estrogen altered an endothelium-dependent effect. No differences in maximum forces were noted with norepinephrine: ED50 OF > OF&E > M. Estrogen treatment, in contrast to KCl, increased sensitivity. Endothelial denudation increased sensitivity but reduced the differences between groups. With ACh relaxation, males were more sensitive than females, and estrogen had no effect. In the abdominal aorta, there were no changes in SM1/SM2 with 17beta-estradiol, and differences in contractility were blunted. In summary, estrogen treatment decreased responses to KCl but increased sensitivity to norepinephrine; male rats always demonstrated the highest contractility. An increase in the COOH-terminal myosin heavy chain isoform SM1-to-SM2 ratio with 17beta-estradiol treatment may underlie the changes observed in contractility.     

Comparison of the phenotypes of the lpxA and lpxD mutants of Escherichia coli

Abstract We compared the phenotype of two thermosensitive Escherichia coli mutants defective in lipid A biosynthesis i.e. SM101 ( lpxA ) and CDH23-213 ( lpxD ). More than 40% of the periplasmic 27-kDa marker enzyme β-lactamase was released from SM101 at 28°C. At this temperature, the mutant still grew with a generation time (67 min), not much longer than that of the parent control strain (57 min). CDH23-213 released β-lactamase only at higher temperatures. SM101 and CDH23-213 were both unable to grow in hypo-osmotic conditions. Derivatives of SM101 and CDH23-213 with mdoA ::Tn 10 had identical phenotypes (including thermosensitivity and defective outer membrane permeability barrier to hydrophobic probes) to those of SM101 and CDH23-213, indicating that the potential loss of membrane-derived oligosaccharides (MDO) did not explain these phenotypic properties. A method for the estimation of lipid A synthesis rate was developed.     

Biodegradation of sulfamethazine by an isolated thermophile–<Emphasis Type="Italic">Geobacillus</Emphasis> sp. S-07

Sulfamethazine (SM2) is an antimicrobial drug that is frequently detected in manure compost, is difficult to degrade at high temperatures and is potentially threatening to the environment. In this study, a thermophilic bacterium was isolated from the activated sludge of an antibiotics pharmaceutical factory; this bacterium has the ability to degrade SM2 at 70?°C, which is higher than the traditional manure composting temperature. The strain S-07 is closely related to Geobacillus thermoleovorans based on its 16S rRNA gene sequence. The optimal conditions for the degradation of SM2 are 70?°C, pH 6.0, 50 rpm rotation speed and 50 mL of culture volume. More than 95% of the SM2 contained in media was removed via co-metabolism within 24 h, which was a much higher percentage than that of the type strain of G. thermoleovorans. The supernatant from the S-07 culture grown in SM2-containing media showed slightly attenuated antibacterial activity. In addition, strain S-07 was able to degrade other sulfonamides, including sulfadiazine, sulfamethoxazole and sulfamerazine. These results imply that strain S-07 might be a new auxiliary bacterial resource for the biodegradation of sulfonamide residue in manure composting.     

Phenocopying action of ether on mn d/SM5-strain Drosophila embryos

Lower sensitivity of the mn d/SM5 strain flies to methyl ether as against the Canton-S flies is established as regarded to induction of bithorax (bx) phenocopies. It is shown that there are no considerable differences in frequencies of bx-phenocopies, abdomen anomalies and ether-induced embryo death between mn d/mn d and mn d/SM5 individuals. It indicates that these parameters are determined by the genotype of the strain on the whole rather than by mn, d, SM5 mutations. Phenocopies of lethal mutations of the pair-rule, Notch, Abnormal abdomen type are established to arise in embryos of both studied strains. In addition disturbances of two other classes are observed among dead embryos of the mn d/SM5 strain. One of them is probably characteristic of SM5/SM5 individuals, the other is phenocopies of mutations disturbing the segment polarity.     

A deterministic mechanism producing the loose coupling phenomenon observed in an actomyosin system

Myosins are molecular motors that convert the chemical energy of ATP into mechanical work called a power stroke. Class II myosin engaged in muscle contraction is reported to show a "loose coupling phenomenon", in which the number of power strokes is greater than the number of ATP hydrolyses. This phenomenon cannot be explained by the lever-arm hypothesis, which is currently accepted as a standard theory for myosin motility. In this paper, a model is proposed to reproduce the loose coupling phenomenon. The model is based on a mechanochemical process called "Driven by Detachment (DbD)" mechanism, which assumes that the energy of the power strokes originates from the potential energy generated by the attractive force between myosin and actin. During the docking process, the potential energy is converted into an intramolecular strain in a myosin molecule, which drives the power stroke after the myosin is firmly attached to an actin filament. The energy of ATP is used to temporarily reduce the attractive force and to increase the potential energy. Therefore, it is not directly linked to the power strokes. When myosin molecules work as an aggregate, the sliding movement of a myosin filament driven by the power strokes of some myosin heads makes other myosin heads that have completed their power strokes detach from the actin without consuming ATP. Under the DbD mechanism, these passively detached myosins can be again engaged in power strokes after the next attachment to actin. As a result, the number of power strokes becomes greater than the number of ATP hydrolyses, and the loose coupling phenomenon will be observed. A theoretical analysis indicates that the efficiency of converting the potential energy into intramolecular elastic energy determines the number of power strokes per each ATP hydrolysis. Computer simulations showed that the DbD mechanism actually produced the loose coupling phenomenon. A critical requirement for this mechanism is that ATP must preferentially facilitate the detachment of myosins that have completed their power strokes, but are still strongly attached to the actin. This requirement may be fulfilled by ATP hydrolysis tightly depending on the conformation of a myosin molecule.     

Reduced interleukin-1 responsiveness in immune system and central nervous system of inbred polydipsic (STR/N) mice

Inbred polydipsic mice (STR/N strain) have primary polydipsia. The previous studies found abnormalities in the central nervous system (CNS), especially in the hypothalamus and circumventricular organ. As a part of pursuing to find the cause of the polydipsia, we investigated immunological characteristics of STR/N mice, using the ICR strain of mice as control. Their thymic subset cells showed that CD4+CD8+ double positive cells were increased, CD4+ single positive cells were decreased and CD5 expression was deficient, compared to ICR mice. T cell proliferative response and interleukin (IL)-2 production caused by IL-1beta stimulation were reduced in STR/N mice than those in the ICR mice. In in vivo studies the degree of thymic atrophy and the increases in serum level of ACTH and corticosterone induced by intraperitoneal IL-1beta injection were much less in STR/N mice than those in controls. Furthermore, adipsic response also induced by IL-1beta injection was greatly reduced compared to their control mice. All these results suggest that the responsiveness to IL-1 is impaired both in the immune system and the CNS of STR/N mice.