Ecological and physiological variance in T-cell mediated immune response in Cory's shearwaters

T-cell mediated immune response (CMI) hasbeen widely studied in relation to individual andfitness components in birds. However, few studieshave simultaneously examined individual and socialfactors and habitat-mediated variance in theimmunity of chicks and adults from the samepopulation and in the same breeding season. Weinvestigated ecological and physiological variancein CMI of male and female nestlings and adults in abreeding population of Cory's Shearwaters(Calonectrisdiomedea) in theMediterranean Sea. Explanatory variables includedindividual traits (body condition, carbon andnitrogen stable isotope ratios, plasma totalproteins, triglycerides, uric acid, osmolarity,β-hydroxy-butyrate, erythrocyte meancorpuscular diameter, hematocrit, andhemoglobin) and burrow traits(temperature, isolation, and physicalstructure). During incubation, immune responseof adult males was significantly greater than thatof females. Nestlings exhibited a lower immuneresponse than adults. Ecological and physiologicalfactors affecting immune response differed betweenadults and nestlings. General linear models showedthat immune response in adult males was positivelyassociated with burrow isolation, suggesting thatmales breeding at higher densities suffer immunesystem suppression. In contrast, immune response inchicks was positively associated with bodycondition and plasma triglyceride levels.Therefore, adult immune response appears to beassociated with social stress, whereas a trade-offbetween immune function and fasting capability mayexist for nestlings. Our results, and those fromprevious studies, provide support for anasymmetrical influence of ecological andphysiological factors on the health of differentage and sex groups within a population, and for theimportance of simultaneously considering individualand population characteristics in intraspecificstudies of immune response.

Ecological and physiological variance in T-cell mediated immune response in Cory's shearwaters

T-cell mediated immune response (CMI) hasbeen widely studied in relation to individual andfitness components in birds. However, few studieshave simultaneously examined individual and socialfactors and habitat-mediated variance in theimmunity of chicks and adults from the samepopulation and in the same breeding season. Weinvestigated ecological and physiological variancein CMI of male and female nestlings and adults in abreeding population of Cory's Shearwaters(Calonectrisdiomedea) in theMediterranean Sea. Explanatory variables includedindividual traits (body condition, carbon andnitrogen stable isotope ratios, plasma totalproteins, triglycerides, uric acid, osmolarity,β-hydroxy-butyrate, erythrocyte meancorpuscular diameter, hematocrit, andhemoglobin) and burrow traits(temperature, isolation, and physicalstructure). During incubation, immune responseof adult males was significantly greater than thatof females. Nestlings exhibited a lower immuneresponse than adults. Ecological and physiologicalfactors affecting immune response differed betweenadults and nestlings. General linear models showedthat immune response in adult males was positivelyassociated with burrow isolation, suggesting thatmales breeding at higher densities suffer immunesystem suppression. In contrast, immune response inchicks was positively associated with bodycondition and plasma triglyceride levels.Therefore, adult immune response appears to beassociated with social stress, whereas a trade-offbetween immune function and fasting capability mayexist for nestlings. Our results, and those fromprevious studies, provide support for anasymmetrical influence of ecological andphysiological factors on the health of differentage and sex groups within a population, and for theimportance of simultaneously considering individualand population characteristics in intraspecificstudies of immune response.

Immunomodulatory effect of mesenchymal stem cells on B cells

The research on T cell immunosuppression therapies has attracted most of the attention in clinical transplantation. However, B cells and humoral immune responses are increasingly acknowledged as crucial mediators of chronic allograft rejection. Indeed, humoral immune responses can lead to renal allograft rejection even in patients whose cell-mediated immune responses are well controlled. On the other hand, newly studied B cell subsets with regulatory effects have been linked to tolerance achievement in transplantation. Better understanding of the regulatory and effector B cell responses may therefore lead to new therapeutic approaches. Mesenchymal stem cells (MSC) are arising as a potent therapeutic tool in transplantation due to their regenerative and immunomodulatory properties.The research on MSCs has mainly focused on their effects onT cells and although data regarding the modulatory effects of MSCs on alloantigen-specific humoral response in humans is scarce, it has been demonstrated that MSCs significantly affect B cell functioning. In the present review we will analyze and discuss the results in this field.

Experimental exposure of the blue mussel (Mytilus edulis, L.) to the toxic dinoflagellate Alexandrium fundyense: Histopathology, immune responses, and recovery

Mussels (Mytilus edulis) were exposed to cultures of the toxic dinoflagellate Alexandrium fundyense or the non-toxic alga Rhodomonas sp. to evaluate the effects of the harmful alga on the mussels and to study recovery after discontinuation of the A. fundyense exposure. Mussels were exposed for 9 days to the different algae and then all were fed Rhodomonas sp. for 6 more days. Samples of hemolymph for hemocyte analyses and tissues for histology were collected before the exposure and periodically during exposure and recovery periods. Mussels filtered and ingested both microalgal cultures, producing fecal pellets containing degraded, partially degraded, and intact cells of both algae. Mussels exposed to A. fundyense had an inflammatory response consisting of degranulation and diapedesis of hemocytes into the alimentary canal and, as the exposure continued, hemocyte migration into the connective tissue between the gonadal follicles. Evidence of lipid peroxidation, similar to the detoxification pathway described for various xenobiotics, was found; insoluble lipofuchsin granules formed (ceroidosis), and hemocytes carried the granules to the alimentary canal, thus eliminating putative dinoflagellate toxins in feces. As the number of circulating hemocytes in A. fundyense-exposed mussels became depleted, mussels were immunocompromised, and pathological changes followed, i.e., increased prevalences of ceroidosis and trematodes after 9 days of exposure. Moreover, the total number of pathological changes increased from the beginning of the exposure until the last day (day 9). After 6 days of the exposure, mussels in one of the three tanks exposed to A. fundyense mass spawned; these mussels showed more severe effects of the toxic algae than non-spawning mussels exposed to A. fundyense. No significant differences were found between the two treatments during the recovery period, indicating rapid homeostatic processes in tissues and circulating hemocytes.

Crucial role of CB(2) cannabinoid receptor in the regulation of central immune responses during neuropathic pain

Neuropathic pain is a clinical manifestation of nerve injury difficult to treat even with potent analgesic compounds. Here, we used different lines of genetically modified mice to clarify the role played by CB2 cannabinoid receptors in the regulation of the central immune responses leading to the development of neuropathic pain. CB2 knock-out mice and wild-type littermates were exposed to sciatic nerve injury, and both genotypes developed a similar hyperalgesia and allodynia in the ipsilateral paw. Most strikingly, knock-outs also developed a contralateral mirror image pain, associated with an enhanced microglial and astrocytic expression in the contralateral spinal horn. In agreement, hyperalgesia, allodynia, and microglial and astrocytic activation induced by sciatic nerve injury were attenuated in transgenic mice overexpressing CB2 receptors. These results demonstrate the crucial role of CB2 cannabinoid receptor in modulating glial activation in response to nerve injury. The enhanced manifestations of neuropathic pain were replicated in irradiated wild-type mice reconstituted with bone marrow cells from CB2 knock-outs, thus demonstrating the implication of the CB2 receptor expressed in hematopoietic cells in the development of neuropathic pain at the spinal cord.

Comparative sensitivity of tumor and non-tumor cell lines as reliable approach for in vitro cytotoxicity screening of lysine-based surfactants with potential pharmaceutical applications

Surfactants are used as additives in topical pharmaceuticals and drug delivery systems. The biocompatibility of amino acid-based surfactants makes them highly suitable for use in these fields, but tests are needed to evaluate their potential toxicity. Here we addressed the sensitivity of tumor (HeLa, MCF-7) and non-tumor (3T3, 3T6, HaCaT, NCTC 2544) cell lines to the toxic effects of lysine-based surfactants by means of two in vitro endpoints (MTT and NRU). This comparative assay may serve as a reliable approach for predictive toxicity screening of chemicals prior to pharmaceutical applications. After 24-h of cell exposure to surfactants, differing toxic responses were observed. NCTC 2544 and 3T6 cell lines were the most sensitive, while both tumor cells and 3T3 fibroblasts were more resistant to the cytotoxic effects of surfactants. IC50-values revealed that cytotoxicity was detected earlier by MTT assay than by NRU assay, regardless of the compound or cell line. The overall results showed that surfactants with organic counterions were less cytotoxic than those with inorganic counterions. Our findings highlight the relevance of the correct choice and combination of cell lines and bioassays in toxicity studies for a safe and reliable screen of chemicals with potential interest in pharmaceutical industry.

New cationic nanovesicular systems containing lysine-based surfactants for topical administration: Toxicity assessment using representative skin cell lines

Many strategies for treating diseases require the delivery of drugs into the cell cytoplasm following internalization within endosomal vesicles. Thus, compounds triggered by low pH to disrupt membranes and release endosomal contents into the cytosol are of particular interest. Cationic nanovesicles have attracted considerable interest as effective carriers to improve the delivery of biologically active molecules into and through the skin. In this study, lipid-based nanovesicles containing three different cationic lysine-based surfactants were designed for topical administration. We used representative skin cell lines and in vitro assays to assess whether the cationic compounds modulate the toxic responses of these nanocarriers. The nanovesicles were characterized in both water and cell culture medium. In general, significant agglomeration occurred after 24 h incubation under cell culture conditions. We found different cytotoxic responses among the formulations, which depended on the surfactant,cell line (3T3, HaCaT, and THP-1) and endpoint assayed (MTT, NRU, and LDH). Moreover, no potential phototoxicity was detected in fibroblast or keratinocyte cells, whereas only a slight inflammatory response was induced, as detected by IL-1a and IL-8 production in HaCaT and THP-1 cell lines, respectively. A key finding of our research was that the cationic charge position and the alkyl chain length of the surfactants determine the nanovesicles resulting toxicity. The charge on the a-amino group of lysine increased the depletion of cell metabolic activity, as determined by the MTT assay, while a higher hydrophobicity tends to enhance the toxic responses of the nanovesicles. The insights provided here using different cell lines and assays offer a comprehensive toxicological evaluation of this group of new nanomaterials.