Carbon-nanoparticle-triggered acute lung inflammation and its resolution are not altered in PPARγ-defective (P465L) mice.

BACKGROUND: The alveolar macrophage (AM) - first line of innate immune defence against pathogens and environmental irritants - constitutively expresses peroxisome-proliferator activated receptor γ (PPARγ). PPARγ ligand-induced activation keeps the AM quiescent, and thereby contributes to combat invaders and resolve inflammation by augmenting the phagocytosis of apoptotic neutrophils and inhibiting an excessive expression of inflammatory genes. Because of these presumed anti-inflammatory functions of PPARγ we tested the hypothesis, whether reduced functional receptor availability in mutant mice resulted in increased cellular and molecular inflammatory response during acute inflammation and/or in an impairment of its resolution. METHODS: To address this hypothesis we examined the effects of a carbon-nanoparticle (CNP) lung challenge, as surrogate for non-infectious environmental irritants, in a murine model carrying a dominant-negative point mutation in the ligand-binding domain of PPARγ (P465L/wt). Animals were instilled intratracheally with Printex 90 CNPs and bronchoalveolar lavage (BAL) was gained 24 h or 72 h after instillation to investigate its cellular and protein composition. RESULTS: Higher BAL cell numbers - due to higher macrophage counts - were found in mutants irrespective of treatment. Neutrophil numbers in contrast were slightly lower in mutants. Intratracheal CNP instillation resulted in a profound recruitment of inflammatory neutrophils into the alveolus, but genotype related differences at acute inflammation (24 h) and resolution (72 h) were not observed. There were no signs for increased alveolar-capillary membrane damage or necrotic cell death in mutants as determined by BAL protein and lactate-dehydrogenase content. Pro-inflammatory macrophage-derived cytokine osteopontin was higher, but galectin-3 lower in female mutants. CXCL5 and lipocalin-2 markers, attributed to epithelial cell stimulation did not differ. CONCLUSIONS: Despite general genotype-related differences, we had to reject our hypothesis of an increased CNP induced lung inflammation and an impairment of its resolution in PPARγ defective mice. Although earlier studies showed ligand-induced activation of nuclear receptor PPARγ to promote resolution of lung inflammation, its reduced activity did not provide signs of resolution impairment in the settings investigated here.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Comparison of particle-exposure triggered pulmonary and systemic inflammation in mice fed with three different diets

<p>Abstract</p> <p>Background</p> <p>Obesity can be linked to disease risks such as diabetes and cardiovascular disorders, but recently, the adipose tissue (AT) macrophage also emerges as actively participating in inflammation and immune function, producing pro- and anti-inflammatory factors. Connections between the AT and chronic lung diseases, like emphysema and asthma and a protective role of adipocyte-derived proteins against acute lung injury were suggested.</p> <p>In this study we addressed the question, whether a diet challenge increases the inflammatory response in the alveolar and the blood compartment in response to carbon nanoparticles (CNP), as a surrogate for ambient/urban particulate air pollutants.</p> <p>Methods</p> <p>Mice were fed a high caloric carbohydrate-rich (CA) or a fat-rich (HF) diet for six weeks and were compared to mice kept on a purified low fat (LF) diet, respectively. Bronchoalveolar lavage (BAL) and blood samples were taken 24 h after intratracheal CNP instillation and checked for cellular and molecular markers of inflammation.</p> <p>Results and discussion</p> <p>The high caloric diets resulted in distinct effects when compared with LF mice, respectively: CA resulted in increased body and fat mass without affecting blood cellular immunity. Conversely, HF activated the blood system, increasing lymphocyte and neutrophil counts, and resulted in slightly increased body fat content. In contrast to higher pro-inflammatory BAL Leptin in CA and HF mice, on a cellular level, both diets did not lead to an increased pro-inflammatory basal status in the alveolar compartment per se, nor did result in differences in the particle-triggered response. However both diets resulted in a disturbance of the alveolar capillary barrier as indicated by enhanced BAL protein and lactate-dehydrogenase concentrations. Systemically, reduced serum Adiponectin in HF mice might be related to the observed white blood cell increase.</p> <p>Conclusion</p> <p>The increase in BAL pro-inflammatory factors in high caloric groups and reductions in serum concentrations of anti-inflammatory factors in HF mice, clearly show diet-specific effects, pointing towards augmented systemic inflammatory conditions. Our data suggest that extended feeding periods, leading to manifest obesity, are necessary to generate an increased susceptibility to particle-induced lung inflammation; although the diet-challenge already was efficient in driving pro-inflammatory systemic events.</p

Early development and the emergence of individual differences in behavior among littermates of wild rabbit pups

International audienceThe ontogeny of associated individual differences in behavior and physiology during early postnatal life, and inparticular the emergence of such differences among litter siblings, has been hardly explored in mammalsunder natural conditions. We studied such within-litter differences in behavior in European rabbit pupsOryctolagus cuniculus prior to weaning, and whether and how these differences co-varied with other individualcharacteristics such as postnatal body temperature and early growth. The study was conducted under seminaturalconditions in a colony of rabbits of wild origin,where the youngwere born and developed in nursery burrows.Weequipped two siblings per litterwith interscapular skin temperature loggers on postnatal day 2 and recordedtemperature profiles for 48 h. Individual body (skin) temperatures of pups within litters were repeatableacross time, indicating the existence of consistent individual differences. Such differences within litters were associatedwithrelative differences in pre-weaning growth, revealing that relativelywarmer pups showed a greaterincrease in body mass during the nest period. Between postnatal days 12 and 17, after the pups had reached adevelopmental stage of greater mobility, we carried out different behavioral tests: a handling-restraint test, anopen field test and a jump-down test from a platform. Individual responses in the former two tests were associated,as those pups showing a quicker struggling response to restraint during handling also exhibited greater exploratoryactivity in the open field. This correlation across contexts suggests the existence of personality types inwild rabbits at an early developmental stage. Furthermore, pups' behavioral responses were strongly associatedwith their relative within-litter body mass at testing. Animals with a lower body mass compared to their siblingsshowed a relatively quicker struggle response to handling restraint and covered a relatively larger distance in theopen field, suggesting greater reactivity and responsiveness of relatively lighter pups in these tests. In contrast,relatively heavier pups jumped sooner from the platform, which may have been due to their greater physicalmaturation. In conclusion, our study shows that individual differences in behavior and associated differencesin body temperature and growth are already present during early postnatal life, although such relationshipscan be easily overlooked, as they predominantly emerge as relative differences among littermates

Differentiation of animals from different age classes by means of pellet size: Assessment of a field method in European rabbits

Estimating population age structures by faecal pellets sizes is a commonly used field method in some mammal species. We examined the validity of this method in European rabbits based on 1113 pellets from 226 animals with known age, by measuring the intra-individual variation in pellet size and studying the explained variance of calibration curves describing the relation between pellet size and individual age. In addition, we applied a simulation model in order to estimate the accuracy of this method. Pellet size showed a high intra-individual variation and was only moderately correlated with the animals' age. Modelling revealed that the population age structure assessed by this method deviated considerably from the given structure, indicating a systematic estimation error. We conclude that this method can lead to strongly biased results, restricting its validity. We provide estimation errors, which might be considered if estimates of age structure in wild rabbits populations based on faecal diameters are conducted.Permission for studies on European rabbits was granted by the government of Middle Franconia (211-3894a). M. Delibes-Mateos is currently holding a Juan de la Cierva research contract awarded by the Spanish Ministry of Science and Innovation and the European Social Fund.Peer Reviewe

Ambient temperature affects postnatal litter size reduction in golden hamsters

International audienceBackground: To better understand how different ambient temperatures during lactation affect survival of young, we studied patterns of losses of pups in golden hamsters (Mesocricetus auratus) at different ambient temperatures in the laboratory, mimicking temperature conditions in natural habitats. Golden hamsters produce large litters of more than 10 young but are also known to wean fewer pups at the end of lactation than they give birth to. We wanted to know whether temperature affects litter size reductions and whether the underlying causes of pup loss were related to maternal food (gross energy) intake and reproductive performance, such as litter growth. For that, we exposed lactating females to three different ambient temperatures and investigated associations with losses of offspring between birth and weaning. Results: Overall, around one third of pups per litter disappeared, obviously consumed by the mother. Such litter size reductions were greatest at 30°C, in particular during the intermediate postnatal period around peak lactation. Furthermore, litter size reductions were generally higher in larger litters. Maternal gross energy intake was highest at 5°C suggesting that mothers were not limited by milk production and might have been able to raise a higher number of pups until weaning. This was further supported by the fact that the daily increases in litter mass as well as in the individual pup body masses, a proxy of mother's lactational performance, were lower at higher ambient temperatures. Conclusions: We suggest that ambient temperatures around the thermoneutral zone and beyond are preventing golden hamster females from producing milk at sufficient rates. Around two thirds of the pups per litter disappeared at high temperature conditions, and their early growth rates were significantly lower than at lower ambient temperatures. It is possible that these losses are due to an intrinsic physiological limitation (imposed by heat dissipation) compromising maternal energy intake and milk production

Stable individual differences in separation calls during early development in cats and mice

International audienceBackground: The development of ethologically meaningful test paradigms in young animals is an essential step in the study of the ontogeny of animal personality. Here we explore the possibility to integrate offspring separation (distress) calls into the study of consistent individual differences in behaviour in two species of mammals, the domestic cat (Felis silvestris catus) and the mound-building mouse (Mus spicilegus). Such vocal responses in young mammals are a potentially useful test option as they represent an important element of mother-offspring communication with strong implications for offspring survival. In addition, the neural control of vocalisation is closely associated with emotional state.esults: We found marked similarities in the pattern of individual responses of the young of both species to separation from their mother and littermates. In the domestic cat as well as in the mound-building mouse, individual differences in the frequency of calls and to a lesser extent in locomotor activity were repeatable across age, indicating the existence of personality types. Such consistencies across age were also apparent when only considering relative individual differences among litter siblings. In both species, however, individual patterns of vocalisation and locomotor activity were unrelated. This suggests that these two forms of behavioural responses to isolation represent different domains of personality, presumably based on different underlying neurophysiological mechanisms.onclusions: Brief separation experiments in young mammals, and particularly the measurement of separation calls, provide a promising approach to study the ontogeny of personality traits. Future long-term studies are needed to investigate the association of these traits with biologically meaningful and potentially repeatable elements of behaviour during later life

Dolphin Welfare Assessment under Professional Care: ‘Willingness to Participate’, an Indicator Significantly Associated with Six Potential ‘Alerting Factors’

International audienceIn dolphinaria, dolphins and their trainers build relationships and bonds due to the nature,closeness and repeatability of their interactions, hence training sessions are deemed appropriate toevaluate dolphin welfare. Qualitative Behavioural Assessments (QBAs) have been used to studyhuman–animal relationships and are included in several animal welfare assessments. We introducehere the first QBA aiming to analyse dolphin–trainer interactions during training sessions in terms ofdolphin welfare. Our results show that “Willingness to Participate” (WtP) was significantly associatedto six other parameters: high-speed approach, high level of excitement, high number of positiveresponses to trainers’ signals, rare refusal to perform certain behaviours, rare spontaneous departurebehaviours and fast approach once the trainer entered into the pool. Therefore, we suggest usingWtP and those “alerting factors” when assessing dolphin–trainer interactions under professionalcare. The evaluation should also consider the time of day, the dolphin’s age, trainer experience level,the nature of the training sessions and to a lesser extent the sex of the dolphins, as contributing andmodulating factors. The factor eye contact has been used in various HARs studies and has beenproven to be a valid indicator in welfare research works, hence potentially deserving further research.These results demonstrate the pertinence and feasibility of this approach, the ease of use of thismethodology by professionals in zoo/aquarium settings and the appropriateness of the obtainedresults within the holistic frame of animal welfare

Major histocompatibility complex variation and age-specific endoparasite load in subadult European rabbits

Genes of the major histocompatibility complex (MHC) play a fundamental role in the vertebrate immune response and are amongst the most polymorphic genes in vertebrate genomes. It is generally agreed that the highly polymorphic nature of the MHC is maintained through host–parasite co-evolution. Two nonexclusive mechanisms of selection are supposed to act on MHC genes: superiority of MHC heterozygous individuals (overdominance) and an advantage for rare MHC alleles. However, the precise mechanisms and their relative importance are still unknown. Here, we examined MHC dependent parasite load in European rabbits (Oryctolagus cuniculus) from a distinct population with low MHC diversity (three alleles, six genotypes). Using a multivariate approach, we tested for associations of individual MHC class II DRB constitution and the rabbits’ intestinal burden with nematodes and coccidia. Rabbits having a particular allele showed lower infestations with hepatic coccidia (E. stiedai). However, a comparison of all six genotypes in the population revealed that carriers of this allele only benefit when they are heterozygous, and furthermore, MHC heterozygosity in general did not affect individual parasite load. In conclusion, this study suggests an immunogenetic basis of European rabbit resistance to hepatic coccidiosis, which can strongly limit survival to maturity in this species. Our study gives a complex picture of MHC–parasite correlations, unveiling the limits of the classical hypotheses of how MHC polymorphism is maintained in natural systems