Homeostatic maintenance of T cells and natural killer cells

Homeostasis in the immune system encompasses the mechanisms governing maintenance of a functional and diverse pool of lymphocytes, thus guaranteeing immunity to pathogens while remaining self-tolerant. Antigen-naïve T cells rely on survival signals through contact with self-peptide-loaded major histocompatibility complex (MHC) molecules plus interleukin (IL)-7. Conversely, antigen-experienced (memory) T cells are typically MHC-independent and they survive and undergo periodic homeostatic proliferation through contact with both IL-7 and IL-15. Also, non-conventional γδ T cells rely on a mix of IL-7 and IL-15 for their homeostasis, whereas natural killer cells are mainly dependent on contact with IL-15. Homeostasis of CD4⁺ T regulatory cells is different in being chiefly regulated by contact with IL-2. Notably, increased levels of these cytokines cause expansion of responsive lymphocytes, such as found in lymphopenic hosts or following cytokine injection, whereas reduced cytokine levels cause a decline in cell numbers.     

Effects of adrenal demedullation combined with chemical sympathectomy on cold-induced responses of endocrine pancreas in rats

Adrenal demedullation combined with chemical sympathectomy with 6-hydroxydopamine (ACS) lowered plasma glucagon and insulin levels in rats. Acute cold exposure increased plasma glucagon in both ACS and control rats, while it increased plasma insulin only in ACS rats. ACS rats responded to cold with a smaller increase in plasma glycerol and a more pronounced elevation of plasma free fatty acids.     

Induction of neovascularization in vivo by glycerol

Glycerol, injected into a site between the femoral vessels of the rat, induced neovascularization, both from the preexisting microcirculation and from the side of the femoral vein facing the artery-vein interstitium where the glycerol was administered. The use of glycerol together with a known angiogenic substance (PGE₂) did not modify the neocapillary density (NCD) obtained with glycerol alone. In contrast, the lower level of NCD achieved with an acylglycerol (triacetylglycerol) was increased when the latter was associated with PGE₂. Values reached were similar to, but never higher than, those for glycerol alone, or combined with PGE₂. The results suggest that glycerol and some substances containing glycerol, amongst which 1-butyrylglycerol has been previously considered¹, may stimulate angiogenesis by a direct or indirect mechanism of action.     

Aquaglyceroporins: implications in adipose biology and obesity

Aquaporins (AQPs) are membrane water/glycerol channels that are involved in many physiological processes. Their primary function is to facilitate the bidirectional transfer of water and small solutes across biological membranes in response to osmotic gradients. Aquaglyceroporins, a subset of the AQP family, are the only mammalian proteins with the ability to permeate glycerol. For a long time, AQP7 has been the only aquaglyceroporin associated with the adipose tissue, which is the major source of circulating glycerol in response to the energy demand. AQP7 dysregulation was positively correlated with obesity onset and adipocyte glycerol permeation through AQP7 was appointed as a novel regulator of adipocyte metabolism and whole-body fat mass. Recently, AQP3, AQP9, AQP10 and AQP11 were additionally identified in human adipocytes and proposed as additional glycerol pathways in these cells. This review contextualizes the importance of aquaglyceroporins in adipose tissue biology and highlights aquaglyceroporins’ unique structural features which are relevant for the design of effective therapeutic compounds. We also refer to the latest advances in the identification and characterization of novel aquaporin isoforms in adipose tissue. Finally, considerations on the actual progress of aquaporin research and its implications on obesity therapy are suggested.     

Physiological roles of glycerol-transporting aquaporins: the aquaglyceroporins

A subclass of aquaporin (AQP) water channels, termed aquaglyceroporins, are also able to transport glycerol and perhaps urea and other small solutes. Although extensive data exist on the physiological roles of aquaporin-facilitated water transport, until recently the biological significance of glycerol transport by the mammalian aquaglyceroporins has been unknown. There is now compelling evidence for involvement of aquaglyceroporin- facilitated glycerol transport in skin hydration and fat cell metabolism. Mice deficient in AQP3 have dry skin, reduced skin elasticity and impaired epidermal biosynthesis. Mice lacking AQP7 manifest progressive adipocyte fat accumulation and hypertrophy. These skin and fat phenotypes are attributable to impaired glycerol transport. A potential implication of these findings is the possibility of modulation of aquaglyceroporin expression or function in the therapy of skin diseases and obesity. Received 20 January 2006; received after revision 21 February 2006; accepted 20 March 2006     

Reactivation by glycerol and ethylene glycol of inactivated delta-aminolevulinic acid synthetase of Rhodopseudomonas spheroides.

Reactivation effects by glycerol and ethylene glycol of inactivated ALA synthetase of R. spheroids were observed. Accompanying the reactivation of the inactivated enzyme, Km value for PLP decreased to levels similar to those of the freshly prepared enzyme.     

A population of human lymphocytes staining for esterases

Summary A population of lymphocytes is found to stain positively for esterases. The positively staining lymphocytes are more predominant among T than B lymphocytes and are significantly increased on stimulation with PHA. Treatment with cholinestrase inhibitors reduces their number significantly.This work was supported by a grant from the Medical Research Council of Canada.     

Renal effects of the inhibitor of thromboxane A2-synthetase OKY-046

Summary Acute renal failure (ARF) was associated with increased urinary thromboxane (TXA₂) excretion and lessened excretion of sodium (U_NaV) and fractional excretion of sodium (FE_Na%). The inhibitor of thromboxane A₂-synthetase OKY-046 enhanced sodium excretion and fractional excretion of sodium in normal and saline loaded animals whereas it partially prevented the reduction in sodium excretion and creatinine clearance and significantly increased fractional excretion of sodium in glycerol treated rats suggesting a partial protection against the development of acute renal failure.Acknowledgment. This work was supported by the Public Benefit Foundation Alexander S. Onassis (G-73). We thank ONO Pharmaceutical Co. Ltd, Kissei Pharmaceutical Co. Ltd, Osaka, Japan, and Dr A Hornych for their generous donations of OKY-046 and anti6keto-PGF_1a antibodies respectively.     

Effects of gastric secretagogues on tissue glycerol in the isolated amphibian gastric mucosa

Histamine and theophylline, two gastric secretagogues, significantly increased tissue glycerol content by 121 and 66%, respectively, in the isolated toad gastric mucosa. This is new evidence in favor of the hypothesis that gastric secretagogues may act via lipid mobilization.     

A population of human lymphocytes staining for esterases.

A population of lymphocytes is found to stain positively for esterases. The positively staining lymphocytes are more predominant among T than B lymphocytes and are significantly increased on stimulation with PHA. Treatment with cholinestrase inhibitors reduces their number significantly.     

Endocannabinoids and β-amyloid-induced neurotoxicity in vivo: effect of pharmacological elevation of endocannabinoid levels

We investigated the involvement of endocannabinoids in the control of neuronal damage and memory retention loss in rodents treated with the β-amyloid peptide (1–42) (BAP). Twelve days after stereotaxic injection of BAP into the rat cortex, and concomitant with the appearance in the hippocampus of markers of neuronal damage, 2-arachidonoyl glycerol, but not anandamide, levels were enhanced in the hippocampus. VDM-11 (5 mg/kg, i.p.), an inhibitor of endocannabinoid cellular reuptake, significantly enhanced rat hippocampal and mouse brain endocannabinoid levels when administered sub-chronically starting either 3 or 7 days after BAP injection and until the 12–14th day. VDM-11 concomitantly reversed hippocampal damage in rats, and loss of memory retention in the passive avoidance test in mice, but only when administered from the 3rd day after BAP injection. We suggest that early, as opposed to late, pharmacological enhancement of brain endocannabinoid levels might protect against β-amyloid neurotoxicity and its consequences. Received 26 January 2006; received after revision 24 March 2006; accepted 12 April 2006     

Glycerin prevents the 'heat-death' of Ehrlich ascites tumor cells

When heated to 45 degrees C for 20 min Ehrlich ascites tumor and NK-lymphoma cells are irreversibly damaged, so that they lose transplantability. The presence of 7-8% glycerol during heat treatment protects EAT cells completely and NK-lymphoma cells partly against this injury.     

Reactivation by glycerol and ethylene glycol of inactivatedδ-aminolevulinic acid synthetase ofRhodopseudomonas spheroides

Summary Reactivation effects by glycerol and ethylene glycol of inactivated ALA synthetase ofR. spheroides were observed. Accompanying the reactivation of the inactivated enzyme, K _m value for PLP decreased to levels similar to those of the freshly prepared enzyme.     

Thymus gland involution induced by lithium chloride

Summary Chronic treatment with lithium chloride produced significant involution of the thymus gland with histological evidence of reduced cellularity due to loss of thymic lymphocytes and a significant reduction in the weight of the gland in normal and adrenalectomized mice. Lithium also increased corticosterone levels in normal mice without changes in adrenal weights. The involution of the thymus gland is most likely due to an effect of lithium on the gland, and it is not mediated by adrenocortical mechanisms or stress.Acknowledgments. We wish to thank Mrs Carroll Masson and Mr W. Resetarits for technical assistance and to Dr B. E. P. Murphy for the radioimmunoassays of corticosterone levels. This work was supported by MRC of Canada, grant MA-5130, and the Department of Psychiatry, MIP, University of Missouri-Columbia, Missouri.     

Studies on the relationships between biotin and the behaviour of B and T lymphocytes in the guinea-pig

Summary In biotin-deficient guinea-pigs the number of circulating neutrophils is increased; lymphocytes carrying B and T markers are decreased. Incubation with biotin increases significantly the number of lymphocytes carrying B and T markers, from biotin-deficient guinea-pigs; no increase was observed when the lymphocytes from normal guinea-pigs were incubated.     

Glycerin prevents the ‘heat-death’ of ehrlich ascites tumor cells

Summary When heated to 45°C for 20 min Ehrlich ascites tumor and NK-lymphoma cells are irreversibly damaged, so that they lose transplantability. The presence of 7–8% glycerol during heat treatment protects EAT cells completely and NK-lymphoma cells partly against this injury.     

A component of polyphloretin phosphate (PPP) may be an alternative substrate for ATP-glycerol transferase

Summary A low molecular weight fraction of a polyphloretin phosphate (PPP) preparation simulated glycerol in a milieu designed for enzymatic assay of glycerol. It is suggested that a component of this PPP mixture is able to act as an alternative substrate for the ATP-glycerol transfer enzyme; it becomes phosphorylated and thus initiates the series of reactions resulting in a increased conversion of NADH to NAD and the observed changes in absorbance.The authors are pleased to acknowledge the support of Dr D.C. Williams, the useful discussion with Dr M. Higgins and Dr J.J.M. Rowe and the generous supply of polyphloretin compounds from A.B. LEO Laboratories, Helsingborg, Sweden.     

Molecular mimicry and the role of B lymphocytes in the processing of autoantigens

The immune system has evolved several mechanisms that provide lymphocytes with the intelligence to ignore self proteins while attacking foreign pathogenic agents. Notably, B and T lymphocytes that encounter self antigen at either the inappropriate levels or affinity are usually instructed to perish or become anergized. However, the presence of autoimmune disease suggests that the induction of self tolerance is not foolproof. In fact, autoreactive cells are now found to be normal inhabitants of the B and T lymphocyte repertoire. This review examines how foreign peptides which resemble self proteins can elicit autoimmunity that is amplified to many sites on a target autoantigen. In particular, B lymphocytes initiated by foreign molecular mimics can process and present self peptides in the shaping of autoimmune T cell responses.     

Na, K ATPase activity during early postnatal development of the rat submandibular gland

The activity of the ouabain-sensitive Na, K ATPase was measured in membrane fractions of the submandibular gland of 1-, 7-, 14- and 21-day-old rats. This activity increased with age and reached adult levels by 21 days.     

Glycerol production byDunaliella

Summary Species of the unicellular algaDunaliella possess outstanding tolerance of a wide range of salinities. They can adapt to grow in salt media which range from less than 0.5 M to saturated salt solutions and withstand enormous osmotic shocks through a unique osmotic adaptation. The osmoregulating mechanism depends on photosynthetic production of glycerol, whose intracellular concentration varies in direct proportion to the extracellular salt concentration and reaches values in excess of 50% of the total dry weight of the cells.Dunaliella, and another halotolerant glycerol producing alga,Asteromonas gracilis, osmoregulate biochemically by controlling glycerol biosynthesis and degradation. 3 new enzymes, NADPH-dihydroxyacetone-reductase, dihydroxyacetone kinase and glycerol-1-phosphatase seem to be involved in the osmoregulatory response via glycerol inDunaliella andAsteromonas. A hypothetical scheme of glycerol metabolism in these algae utilizing these enzymes is presented. Growth studies ofDunaliella indoors and outdoors showed that salt concentrations favoring maximal glycerol productivity are not identical with those required for maximal algal productivity. Maximal yield of glycerol occurred around 2 M NaCl while maximal algal productivity occurred below 0.5 M NaCl. Observed yields of glycerol inDunaliella culture outdoors are compared with theoretically calculated maximal yield.