Granulocyte-macrophage colony-stimulating factor protects dendritic cells from liposome-encapsulated dichloromethylene diphosphonate-induced apoptosis through a Bcl-2-mediated pathway

Liposome-encapsulated dichloromethylene diphosphonate (L-MDP) has been used for depleting cells of the monocyte-macrophage lineage. We have undertaken this study to investigate whether dendritic cells are susceptible to this liposome-encapsulated compound. Dendritic cells were cultured in the presence of L-MDP and further processed for apoptosis detection. The highly characteristic DNA cleavage into oligonucleosome-sized fragments, incorporation of biotinylated dUTP into DNA strand breaks and the typical ultrastructural features of apoptosis were evident in dendritic cells exposed to the drug. More importantly, we demonstrated that granulocyte-macrophage colony-stimulating factor protects dendritic cells not only from apoptosis induced by the exogenous compound but also from spontaneous apoptosis. Western blot analysis revealed that this protection was tightly correlated with the activation of a Bcl-2-mediated pathway. Regulation of the apoptotic threshold of dendritic cells will be advantageous for the generation of new insights in immunotherapy.     

Domiciliary biting frequency and blood ingestion of the Chagas's disease vector Rhodnius prolixus Ståhl (Hemiptera: Reduviidae), in Venezuela

Demolition of a rural house in the State of Cojedes, Venezuela, provided a collection of 7.934 Rhodnius prolixus of which a random sample of 1,415 was weighed within 48 hours. The field weights, coupled with laboratory information of weight loss (in %) with time, average blood ingestion and meal size sufficient to promote moulting, were used to estimate biting rate under domiciliary conditions. The results show that in this particularly highly infested house, the R. prolixus population bites, on the average, at a rate of 58 times/person/day, draining blood at a rate of about 100 cm3/person/month; this meant a total of 1.2 litres/month from the 11 people inhabiting the house. It was found that the more advanced R. prolixus is in its development, the more aggressive it is in securing its meal: 15, 25, 30, 59 and 77% of fed insects of instar 1 through 5, respectively, were able to achieve moulting with only one meal. Applying the estimated biting rate to R. prolixus collections of other 13 demolished houses, with more typical insect population densities, an average biting rate of 9 bites/person/day was obtained; this value was, however, extremely variable, ranging from 0.2 bites/person/day (once every five days) to 33 bites/person/day.     

The coming of age of galectins as immunomodulatory agents: impact of these carbohydrate binding proteins in T cell physiology and chronic inflammatory disorders

Immune cell homoeostasis is attributed to multiple distinct safety valves that are interconnected and intervene at defined checkpoints of the life cycle of immunocytes to guarantee clonal expansion and functional inactivation of self-reactive potentially autoaggressive lymphocytes. Galectins, animal lectins defined by shared consensus amino acid sequence and affinity for beta-galactose containing oligosaccharides, are found on various cells of the immune system, and their expression is associated with the differentiation and activation status of these cells. Over the past few years, galectins have been implicated in the regulation of many aspects of T cell physiology such as cell activation, differentiation, and apoptosis. In addition, a growing body of experimental evidence indicates that galectins may play critical roles in the modulation of chronic inflammatory disorders, autoimmunity, and cancer. Given the increased interest of immunologists in this field, the growing body of information raised during the past few years and the potential use of galectins as novel anti-inflammatory agents or targets for immunosuppressive drugs, we will summarise recent advances on the role of galectins in different aspects of T cell physiology and their impact in the development and/or resolution of chronic inflammatory disorders, autoimmunity, and cancer.     

The cortisol response to desipramine in endogenous depressives and normal controls: preliminary findings

Plasma cortisol levels were monitored for 2 hours after an intramuscular injection of 75 mg desipramine in 13 endogenous depressives and 20 normal controls. Endogenous depressives had a significantly reduced cortisol response in comparison to normal controls, not explained by sex, age, or baseline cortisol differences between groups. A lack of a cortisol rise of 1.5 micrograms/dl above baseline by 45 minutes discriminated best, with 7 of 13 depressives (55%) being identified in contrast to only 1 of 20 normals (5%). The results suggest that this may be a useful biological test with acceptable sensitivity (55%) and excellent specificity (95%). Furthermore, these data suggest that norepinephrine may be stimulatory to cortisol in man.     

Immunosynapse formation coincides with rapid activation of NK cells by syngeneic T cells and correlates with clustering of MHC class I

T cells cultured for 3 h with antigen-presenting cells (APCs) stimulated syngeneic IL-2-activated NK cells as measured via a standard chromium-release assay. Discrete caps containing both TCR and MHC-I had formed on the surface of these activated T cells. When conjugates were formed between NK cells and these activated T cells, >80% of the contact sites were in the MHC-I(dim) region outside the TCR-MHC-I cap. Stimulation with phorbol myristate acetate plus Ionomycin, which bypasses the need for cell surface events during activation, did not induce either cap formation or NK cell activation. Further, the addition of the protein transport inhibitor Brefeldin A did not block activation of NK cells. MHC-I is the major inhibitory ligand recognized by NK cells. One possible mechanism for the activation of NK cells by TCR-MHC-I-capped T cells is that aggregation of MHC-I into one region leaves the remaining T cell surface denuded of ligands for NK-inhibitory receptors. As a test of this hypothesis, we aggregated MHC-I on T cells with plate-bound anti-MHC-I mAb. This treatment conferred upon the T cells the capacity to activate NK cells, suggesting that MHC-I clustering could contribute to the observed phenomenon.