The role of platelet CD154 in the modulation in adaptive immunity

Platelets’ primary role is hemostasis. However, a growing body of research has demonstrated that platelets are integral to the initiation of an inflammatory response and are potent effector cells of the innate immune response. Activated platelets express CD154, a molecule critical to adaptive immune responses, which has been implicated in platelet-mediated modulation of innate immune responses and inflammation. Recent studies utilizing CD154 knockout mice extend the role of platelet-derived CD154 to the modulation of adaptive immune response by enhancing antigen presentation, improving CD8⁺ T cell responses, and playing a critical function in T-dependent humoral immunity under physiological conditions. Together these data provide a basis for the expansion of the current paradigm of B cell activation and germinal center formation to include a role for platelets.     

Prevalence of self-reported food allergy in American adults and use of food labels

BACKGROUND: Few population-based studies in the United States have determined the prevalence of food allergy in adults and the problems these individuals might have with reading food labels. OBJECTIVE: The objectives of this study are to report the prevalence of self-reported food allergy, to identify the characteristics of food allergy reactions, and to describe the use of labels among adults with food allergy. METHODS: Questions from the US Food and Drug Administration's 2001 Food Safety Survey were analyzed to determine the prevalence of food allergy and opinions about food labels in the management of food allergy. RESULTS: The prevalence of self-reported food allergy is 9.1% among all survey respondents, with 5.3% of all respondents reporting a doctor-diagnosed food allergy. The prevalence of food allergy to the 8 most common allergens (peanut, tree nuts, egg, milk, wheat, soybeans, fish, and crustacean shellfish) is self-reported as 2.7% among respondents with doctors' diagnoses. Several label issues, such as words on some ingredient lists being too technical or hard to understand and food labels not always alerting persons to new ingredients, were reported as serious or very serious obstacles for managing an allergy. CONCLUSION: The prevalence of self-reported doctor-diagnosed food allergy among US adults is 5.3%, and a large portion of adults with food allergy found certain label issues a serious problem for managing their food allergy. CLINICAL IMPLICATIONS: The findings provide a needed source of population-based prevalence data of food allergy among US adults. Label issues identified are useful in understanding the difficulties of managing a food allergy.     

Multi-Scale Computational Model of Fuel Homeostasis During Exercise: Effect of Hormonal Control

A mathematical model of the whole-body metabolism is developed to predict fuel homeostasis during exercise by using hormonal control over cellular metabolic processes. The whole body model is composed of seven tissue compartments: brain, heart, liver, GI (gastrointestinal) tract, skeletal muscle, adipose tissue, and “other tissues”. Each tissue compartment is described by dynamic mass balances and major cellular metabolic reactions. The glucagon–insulin controller is incorporated into the whole body model to predict hormonal changes during exercise. Moderate [150 W power output at 60% of peak oxygen consumption (VO_2max)] exercise for 60 min was implemented by increasing ATP utilization rates in heart and skeletal muscle. Arterial epinephrine level was given as an input function, which directly affects heart and skeletal muscle metabolism and indirectly other tissues via glucagon–insulin controller. Model simulations were validated with experimental data from human exercise studies. The exercise induced changes in hormonal signals modulated metabolic flux rates of different tissues in a coordinated way to achieve glucose homeostasis, demonstrating the efficacy of hormonal control over cellular metabolic processes. From experimental measurements of whole body glucose balance and arterial substrate concentrations, this model could predict the dynamic changes of hepatic glycogenolysis and gluconeogenesis, which are not easy to measure experimentally, suggesting the higher contribution of glycogenolysis (∼75%). In addition, it could provide dynamic information on the relative contribution of carbohydrates and lipids for fuel oxidation in skeletal muscle. Model simulations indicate that external fuel supplies from other tissue/organ systems to skeletal muscle become important for prolonged exercise emphasizing the significance of interaction among tissues. In conclusion, this model can be used as a valuable complement to experimental studies due to its ability to predict what is difficult to measure directly, and usefulness to provide information about dynamic behaviors.     

Evaluating feeding as unconditioned stimulus for conditioning of an endocrine effect in Nile tilapia

This study tested the adequacy of feeding as an unconditioned stimulus (US) to condition an endocrine response (plasma cortisol increase) in the cichlid fish Nile tilapia (Oreochromis niloticus). In a first study, conditioning was confirmed in grouped fish in the only experiment using single-held Nile tilapia. In this test a conditioned stimulus (CS - aeration off) was associated with a stressor (air emersion for 2 min- US). We then assessed whether several events of paired CS-US resulted in a conditioned endocrine response (CR), in this case an increase in plasma cortisol after presentation of the CS only. Before testing feeding as US, the postprandial or social holding condition for feeding effects on cortisol levels was tested. Nile tilapia showed increased cortisol after feeding associated to social context (grouped fish), but not to food only (single-held fish). In a third study, feeding was tested as US in an experiment similar to the first study but an increase in feeding-induced cortisol could not be conditioned. The absence of CR suggests that the stressor affects acquisition of this response, which may be a consequence of stimulus intensity or biological relevance. This study expands the recently reported Pavlovian conditioning paradigm for endocrine response in fish.     

Treatment of autoimmune disease: time for a paradigm shift?

Current treatment of human autoimmune diseases (AIDs) was developed empirically and relies mostly on non-selective suppression of the immune system. Traditional non-selective immunosuppressants such as corticosteroids, cyclophosphamide, and methotrexate and more novel means such as monoclonal antibodies to CD3, CD4, or CD25 do not discriminate between pathogenic and beneficial T cells. Importantly, the severe side effects seen with current therapies are related to the fact that these treatments not only suppress the pathogenic disease-inducing cells, but also cells influential in combating infections and killing malignant cells. Severe infections and malignancies are the inevitable result of non-selective immune suppression. Many of the novel forms of therapy of AID were developed in experimental animals, and their translation to the human disease was associated with the revelation of unexpected and sometimes catastrophic side effects. These surprises underscore the major differences between the relative simplicity of the experimental model and the complexity of the human disease. How can this current state of treatment of AID be improved? Which principles should guide us in the design of new treatments? This review attempts to offer a new look at these questions.     

Permissive role of calcium on regulatory volume decrease in freshly isolated mouse cholangiocytes

Calcium (Ca²⁺) pathways are important in cell volume regulation in many cells, but its role in volume regulatory processes in cholangiocytes is unclear. Thus, we have investigated the role of Ca²⁺ in regulatory volume decrease (RVD) in cholangiocytes using freshly isolated bile duct cell clusters (BDCCs) from normal mouse. No significant increase in [Ca²⁺]_i was observed during RVD, while ionomycin and ATP showed significant increases. Confocal imaging also showed no significant changes in the levels or distributions of intracellular Ca²⁺ during RVD. Cell volume study by quantitative videomicroscopy indicated that removal and chelation of extracellular Ca²⁺ by ethylene glycol-bis (β-aminoethyl ether)-N,N,N-tetraacetic acid (EGTA) or administration of nifedipine did not affect RVD but verapamil significantly inhibited the RVD. Moreover, Ca²⁺ agonists or inhibitors of Ca²⁺ release from intracellular stores had no significant effect on RVD. However, 1,2-bis (2-aminophenoxy) ethane-N,N,N′N′-tetraacetic acid-AM (BAPTA-AM) showed significant decreases in [Ca²⁺]_i and significantly inhibited RVD, which was reversed with coadministration of valinomycin, suggesting that BAPTA-AM-induced inhibition is due to potassium conductance or other cellular processes requiring permissive [Ca²⁺]_i. These findings indicate that an increase in [Ca²⁺]_i or extracellular Ca²⁺ is not required for RVD but Ca²⁺ has a permissive role in RVD of mouse cholangiocytes.     

GITR/GITRL: more than an effector T cell co-stimulatory system

Glucocorticoid-induced TNFR-related protein (GITR) is a member of the TNFR superfamily, expressed in several cells and tissues including T lymphocytes, NK cells and antigen-presenting cells (APC). GITR activation, upon interaction with its ligand (GITRL), functions as a co-activating signal. GITRL is mainly expressed on APC and GITR/GITRL interaction is important for the development of immune response. This review summarizes recent results about the GITR/GITRL system, focusing on the interplay between APC, effector and regulatory T cells.