Dendritic cell-bound IgE functions to restrain allergic inflammation at mucosal sites.

Antigen-mediated cross-linking of Immunoglobulin E (IgE) bound to mast cells/basophils via FcɛRI, the high affinity IgE Fc-receptor, is a well-known trigger of allergy. In humans, but not mice, dendritic cells (DCs) also express FcɛRI that is constitutively occupied with IgE. In contrast to mast cells/basophils, the consequences of IgE/FcɛRI signals for DC function remain poorly understood. We show that humanized mice that express FcɛRI on DCs carry IgE like non-allergic humans and do not develop spontaneous allergies. Antigen-specific IgE/FcɛRI cross-linking fails to induce maturation or production of inflammatory mediators in human DCs and FcɛRI-humanized DCs. Furthermore, conferring expression of FcɛRI to DCs decreases the severity of food allergy and asthma in disease-relevant models suggesting anti-inflammatory IgE/FcɛRI signals. Consistent with the improved clinical parameters in vivo, antigen-specific IgE/FcɛRI cross-linking on papain or lipopolysaccharide-stimulated DCs inhibits the production of pro-inflammatory cytokines and chemokines. Migration assays confirm that the IgE-dependent decrease in cytokine production results in diminished recruitment of mast cell progenitors; providing a mechanistic explanation for the reduced mast cell-dependent allergic phenotype observed in FcɛRI-humanized mice. Our study demonstrates a novel immune regulatory function of IgE and proposes that DC-intrinsic IgE signals serve as a feedback mechanism to restrain allergic tissue inflammation.

Absence of heme oxygenase-1 expression in the lung parenchyma exacerbates endotoxin-induced acute lung injury and decreases surfactant protein-B levels.

Acute respiratory distress syndrome (ARDS) is a devastating disease process characterized by severe acute lung injury, inflammatory cell recruitment to the lung, upregulation of pro-inflammatory cytokines and increased oxidative stress. Epithelial cell injury, diffuse alveolar damage and surfactant dysfunction ensue leading to refractory hypoxemic respiratory failure. There are no specific effective therapies for ARDS and novel therapeutic approaches are desperately needed. In this study we assessed the role of the cytoprotective and anti-inflammatory enzyme heme oxygenase (HO)-1 in a model of nebulized endotoxin-induced acute lung injury. HO-1 null (HO-1(-/-)) mice exhibited severe physiologic lung dysfunction following lipopolysaccharide (LPS) nebulization, but had similar inflammatory responses as wild-type (WT) mice. However, a dramatic reduction in surfactant protein-B (SP-B) expression was observed in the lungs of LPS-treated HO-1(-/-) mice compared with similarly treated WT mice. Using reciprocal bone marrow transplantation (BMT) to generate HO-1-chimeric mice, we found that absence of HO-1 in the lung parenchyma, not in bone marrow-derived inflammatory cells, was responsible for enhanced SP-B downregulation and severe physiologic lung dysfunction. These findings have implications for our understanding of the pathophysiology of ARDS and may guide future therapeutic strategies.

Deep venous thrombosis: early discharge strategies and outpatient management.

Conventional management of acute deep venous thrombosis (DVT) consists of initiating continuous infusion intravenous unfractionated heparin (UFH) for 5 days in the hospital as well as warfarin. Low-molecular-weight heparins (LMWHs) appear to confer similar protection against recurrent DVT compared with UFH but exhibit prolonged bioavailability; increased ease of dosing, and fewer side effects. The advent of LMWH has resulted in increased numbers of patients undergoing initial management of acute DVT with only several days of hospitalization. While 3-month follow-up studies with LMWH demonstrate similar efficacy and safety to UFH, longer term experience with these new agents is necessary to determine their optimal use and safety. We suggest a system for triage in the initial management of DVT patients for: (1) complete outpatient management with LMWH, or (2) short-term hospitalization for initiation of LMWH, or (3) 5-day hospitalization for treatment with UFH. A review of DVT management with LMWH and algorithms for each of these pathways are provided.

The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations.

In this article, we attempt to distinguish between the properties of moderator and mediator variables at a number of levels. First, we seek to make theorists and researchers aware of the importance of not using the terms moderator and mediator interchangeably by carefully elaborating, both conceptually and strategically, the many ways in which moderators and mediators differ. We then go beyond this largely pedagogical function and delineate the conceptual and strategic implications of making use of such distinctions with regard to a wide range of phenomena, including control and stress, attitudes, and personality traits. We also provide a specific compendium of analytic procedures appropriate for making the most effective use of the moderator and mediator distinction, both separately and in terms of a broader causal system that includes both moderators and mediators.

Young adults' caregiving and the age level of a potential recipient.

The hypothesis that two caregiving tendencies are affected by the age of potential recipients was investigated in two experiments. In Experiment 1, two matched groups of 40 young adults selected from 16 pairs of either facial profile drawings or age-labels (e.g., "2-year-old") those individuals that they would feel most compelled to protect (i.e., the most "defense-provoking" in each pair). Both groups tended to select younger and more elderly individuals over more middle-aged ones. In Experiment 2, two more matched groups of 40 adults rated the defense-provokingness or the cuddliness of a series of facial profile drawings showing a male at eight ages, from newborn to 70 years old. Although rated cuddliness decreased as portrayed age increased from age 6 months onward, rated defense-provokingness decreased with age from birth to 35 years, but increased thereafter. These results are generally consistent with the expectation that adults' tendency to protect or cuddle others varies in accordance with the typical neediness of individuals of different age levels for these forms of care.

Self-evaluation, social reinforcement, and academic achievement of black and white schoolchildren.

Black and white male schoolchildren covertly evaluated their own performance at a verbal task administered by black and white male experimenters. It was hypothesized that academically successful children would be predisposed to appraise themselves favorably, whereas relatively unsuccessful pupils would be biased toward self-criticism. The covert self-evaluations were assumed to represent at internalization of early experiences of predominantly positive or negative social reinforcement from adult socializing agents. The predicition for self-criticism was upheld in the white experimenter condition but not in the black experimenter condition. Relationships consistent with the theory were found between subjects' self-appraisals and their retrospective reports of positive and negative reinforcements received from parents and teachers in various typical situations. These relationships were more evident for black subjects than for white subjects. The extent to which children's self-praise and self-criticism mediated affect was assessed by means of a color conditioning technique. Contrary to predicition, possibly due to the easy nature of the experimental task.