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Background: Excessive alcohol intake is associated with adverse immune response-related effects, however, acute and chronic abuse differently modulate monocyte activation. In this study, we have evaluated the phenotypic and functional changes of monocytes in acutely intoxicated healthy volunteers (HV).
Methods: Twenty-two HV consumed individually adjusted amounts of alcoholic beverages until reaching a blood alcohol level of 1‰ after 4h (T4). Peripheral blood was withdrawn before and 2h (T2), 4h (T4), 6h (T6), 24h (T24), and 48h (T48) after starting the experiment and stained for CD14, CD16 and TLR4. CD14brightCD16-, CD14brightCD16+ and CD14dimCD16+ monocyte subsets and their TLR4 expression were analyzed by flow cytometry. Inflammasome activation via caspase-1 in CD14+ monocytes was measured upon an ex vivo in vitro LPS stimulation. Systemic IL-1β and adhesion capacity of isolated CD14+ monocytes upon LPS stimulation were evaluated.
Results: The percentage of CD14+ monocyte did not change following alcohol intoxication, whereas CD14brightCD16- monocyte subset significantly increased at T2 and T24, CD14brightCD16+ at T2, T4 and T6 and CD14dimCD16+ at T4 and T6. The relative fraction of TLR4 expressing CD14+ monocytes as well as the density of TLR4 surface presentation increased at T2 and decreased at T48 significantly. TLR4+CD14+ monocytes were significantly enhanced in all subsets at T2. TLR4 expression significantly decreased in CD14brightCD16- at T48, in CD14brightCD16+ at T24 and T48, increased in CD14dimCD16+ at T2. IL-1β release upon LPS stimulation decreased at T48, correlating with TLR4 receptor expression. Alcohol downregulated inflammasome activation following ex vivo in vitro stimulation with LPS between T2 and T48 vs. T0. The adhesion capacity of CD14+ monocytes decreased from T2 with significance at T4, T6 and T48. Following LPS administration, a significant reduction of adhesion was observed at T4 and T6.
Conclusions: Alcohol intoxication immediately redistributes monocyte subsets toward the pro-inflammatory phenotype with their subsequent differentiation into the anti-inflammatory phenotype. This is paralleled by a significant functional depression, suggesting an alcohol-induced time-dependent hyporesponsiveness of monocytes to pathogenic triggers.
Sepsis is a serious clinical condition which can cause life-threatening organ dysfunction, and has limited therapeutic options. The paradigm of limiting excessive inflammation and promoting anti-inflammatory responses is a simplified concept. Yet, the absence of intrinsic anti-inflammatory signaling at the early stage of an infection can lead to an exaggerated activation of immune cells, including monocytes and macrophages. There is emerging evidence that endogenous molecules control those mechanisms. Here we aimed to identify and describe the dynamic changes in monocyte and macrophage subsets and lung damage in CL57BL/6N mice undergoing blunt chest trauma with subsequent cecal ligation and puncture. We showed that early an increase in systemic and activated Ly6C+CD11b+CD45+Ly6G− monocytes was paralleled by their increased emigration into lungs. The ratio of pro-inflammatory Ly6ChighCD11b+CD45+Ly6G− to patrolling Ly6ClowCD11b+CD45+Ly6G− monocytes significantly increased in blood, lungs and bronchoalveolar lavage fluid (BALF) suggesting an early transition to inflammatory phenotypes during early sepsis development. Similar to monocytes, the level of pro-inflammatory Ly6ChighCD45+F4/80+ macrophages increased in lungs and BALF, while tissue repairing Ly6ClowCD45+F4/80+ macrophages declined in BALF. Levels of inflammatory mediators TNF-α and MCP-1 in blood and RAGE in lungs and BALF were elevated, and besides their boosting of inflammation via the recruitment of cells, they may promote monocyte and macrophage polarization, respectively, toward the pro-inflammatory phenotype. Neutralization of uteroglobin increased pro-inflammatory cytokine levels, activation of inflammatory phenotypes and their recruitment to lungs; concurrent with increased pulmonary damage in septic mice. In in vitro experiments, the influence of uteroglobin on monocyte functions including migratory behavior, TGF-β1 expression, cytotoxicity and viability were proven. These results highlight an important role of endogenous uteroglobin as intrinsic anti-inflammatory signal upon sepsis-induced early lung injury, which modules the early monocyte/macrophages driven inflammation.
Severe traumatic injury induces phenotypic and functional changes of neutrophils and monocytes
(2021)
Background: Severe traumatic injury has been associated with high susceptibility for the development of secondary complications caused by dysbalanced immune response. As the first line of the cellular immune response, neutrophils and monocytes recruited to the site of tissue damage and/or infection, are divided into three different subsets according to their CD16/CD62L and CD16/CD14 expression, respectively. Their differential functions have not yet been clearly understood. Thus, we evaluated the phenotypic changes of neutrophil and monocyte subsets among their functionality regarding oxidative burst and the phagocytic capacity in severely traumatized patients. Methods: Peripheral blood was withdrawn from severely injured trauma patients (TP; n = 15, ISS ≥ 16) within the first 12 h post-trauma and from healthy volunteers (HV; n = 15) and stimulated with fMLP and PMA. CD16dimCD62Lbright (immature), CD16brightCD62Lbright (mature) and CD16brightCD62Ldim (CD62Llow) neutrophil subsets and CD14brightCD16− (classical), CD14brightCD16+ (intermediate) and CD14dimCD16+ (non-classical) monocyte subsets of HV and TP were either directly analyzed by flow cytometry or the examined subsets of HV were sorted first by fluorescence-activated cell sorting and subsequently analyzed. Subset-specific generation of reactive oxygen species (ROS) and of E. coli bioparticle phagocytosis were evaluated. Results: In TP, the counts of immature neutrophils were significantly increased vs. HV. The numbers of mature and CD62Ldim neutrophils remained unchanged but the production of ROS was significantly enhanced in TP vs. HV and the stimulation with fMLP significantly increased the generation of ROS in the mature and CD62Ldim neutrophils of HV. The counts of phagocyting neutrophils did not change but the mean phagocytic capacity showed an increasing trend in TP. In TP, the monocytes shifted toward the intermediate phenotype, whereas the classical and non-classical monocytes became less abundant. ROS generation was significantly increased in all monocyte subsets in TP vs. HV and PMA stimulation significantly increased those level in both, HV and TP. However, the PMA-induced mean ROS generation was significantly lower in intermediate monocytes of TP vs. HV. Sorting of monocyte and neutrophil subsets revealed a significant increase of ROS and decrease of phagocytic capacity vs. whole blood analysis. Conclusions: Neutrophils and monocytes display a phenotypic shift following severe injury. The increased functional abnormalities of certain subsets may contribute to the dysbalanced immune response and attenuate the antimicrobial function and thus, may represent a potential therapeutic target. Further studies on isolated subsets are necessary for evaluation of their physiological role after severe traumatic injury.
A statewide survey of Wisconsin’s Nemonychidae and Anthribidae (Coleoptera: Curculionoidea) was conducted over one full (2012) and two partial (2011, 2013) fi eld seasons. Specimens were collected using a variety of techniques. Two species of the nemonychid genus Cimberis and 22 species of Anthribidae in 13 genera are now confi rmed. Generic and species-level keys for Wisconsin species are provided along with generic and species diagnoses. Species treatments also include a synonymy, a description, and information on natural history, phenology, distribution and collecting methods. Dorsal and lateral habitus images are also provided for most of the species.
A statewide survey of Wisconsin’s Attelabidae (Coleoptera: Curculionoidea) was conducted over one full (2012) and two partial (2011, 2013) field seasons. Specimens were collected using a variety of techniques. Fourteen species of Attelabidae in nine genera placed in two subfamilies are now recorded from Wisconsin, with five new state species records and 117 new Wisconsin county records. Generic and specieslevel keys for Wisconsin attelabid species are provided along with generic and species diagnoses. Species treatments also include a synonymy, a description, and information on natural history, phenology, distribution and collecting methods. Dorsal and lateral habitus images are also provided for each species.
Les études critiques sur Gabriela Zapolska (1857-1921), féministe polonaise aux brillants et multiples talents littéraires, ont systématiquement relevé dans ses oeuvres son goût passionné pour les couleurs (impressionnisme) et les formes (beauté et laideur du corps féminin). Dans cet article, nous montrerons que Zapolska n'accordait pas moins d'importance à la musicalité du monde qu'à sa beauté plastique: le son dans toutes ses variations et gradations accompagne le parcours de ses protagonistes féminines dans leur quête d'identité. Murmures ou rires révèlent déjà leur féminité, mais ne suffisent encore pas pour lui permettre de s'épanouir. Le travail de libération ne s'accomplit que grâce à la musique. La réciprocité entre la féminité et la musique est posée comme allant de soi: l'expression par la voix ou l'instrument devient l'expression d'une essence cachée et matrilinéaire de l'existence. Pour Zapolska, la musicalité du monde est genrée et elle est marquée d'une signature féminine.
Nina Janich ist Professorin am Institut für Sprach- und Literaturwissenschaft der Technischen Universität Darmstadt. Zu ihren Forschungsgebieten zählen Fragen der Sprachkultur und Sprachkritik sowie Sprachanwendung in der Wissenschaft. Zudem ist sie Jury-Sprecherin der sprachkritischen Aktion "Unwort des Jahres".
This paper compares secondary predication constructions (including small clause complements, resultatives, and/or depictives) in English and Korean and argues that these two typologically different languages employ different modes of satisfying the Case Filter (Chomsky 1981) with regard to the Case of the subjects of secondary predication constructions. More specifically, we argue that the subject of the secondary predicate in English is Accusative Case-marked by the higher governing verb, while that in Korean is Nominative Case-marked by default. Evidence for default Nominative Case will be provided from Korean and other languages.
This study focuses on two German dictionaries published in the Bohemian Lands during the 19th century, whose titles show their relatedness to language purism. In the first part of the study, both dictionaries are presented and compared based on various criteria such as their authors' motivation for publishing them and the presence of any aspects of Germanisation processes. The second part contains an analysis of two parts of the dictionaries; the aim is to examine the dictionary entries and identify the authors' personal stance on language purism.