Inhibition of FcepsilonRI-dependent mediator release and calcium flux from human mast cells by sialic acid-binding immunoglobulin-like lectin 8 engagement

BACKGROUND: Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of glycan-binding inhibitory receptors, and among them, Siglec-8 is selectively expressed on human eosinophils, basophils, and mast cells. On eosinophils, Siglec-8 engagement induces apoptosis, but its function on mast cells is unknown. OBJECTIVE: We sought to study the effect of Siglec-8 engagement on human mast cell survival and mediator release responses. METHODS: Human mast cells were generated from CD34+ precursors. Apoptosis was studied by using flow cytometry. Mast cell mediator release or human lung airway smooth muscle contraction was initiated by FcepsilonRI cross-linking with or without preincubation with Siglec-8 or control antibodies, and release of mediators was analyzed along with Ca++ flux. RBL-2H3 cells transfected with normal and mutated forms of Siglec-8 were used to study how Siglec-8 engagement alters mediator release. RESULTS: Siglec-8 engagement failed to induce human mast cell apoptosis. However, preincubation with Siglec-8 mAbs significantly (P < .05) inhibited FcepsilonRI-dependent histamine and prostaglandin D(2) release, Ca++ flux, and anti-IgE-evoked contractions of human bronchial rings. In contrast, release of IL-8 was not inhibited. Siglec-8 ligation was also shown to inhibit beta-hexosaminidase release and Ca++ flux triggered through FcepsilonRI in RBL-2H3 cells transfected with full-length human Siglec-8 but not in cells transfected with Siglec-8 containing a tyrosine to phenylalanine point mutation in the membrane-proximal immunoreceptor tyrosine-based inhibitory motif domain. CONCLUSION: These data represent the first reported inhibitory effects of Siglec engagement on human mast cells.

Human basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-33

In mice, interleukin-18 (IL-18) regulates Th1- or Th2-type immune responses depending on the cytokine environment and effector cells involved, and the ST2-ligand, IL-33, primarily promotes an allergic phenotype. Human basophils, major players in allergic inflammation, constitutively express IL-18 receptors, while ST2 surface expression is inducible by IL-3. Unexpectedly, freshly isolated basophils are strongly activated by IL-33, but, in contrast to mouse basophils, do not respond to IL-18. IL-33 promotes IL-4, IL-13 and IL-8 secretion in synergy with IL-3 and/or FcepsilonRI-activation, and enhances FcepsilonRI-induced mediator release. These effects are similar to that of IL-3, but the signaling pathways engaged are distinct because IL-33 strongly activates NF-kappaB and shows a preference for p38 MAP-kinase, while IL-3 acts through Jak/Stat and preferentially activates ERK. Eosinophils are the only other leukocyte-type directly activated by IL-33, as evidenced by screening of p38-activation in peripheral blood cells. Only upon CD3/CD28-ligation, IL-33 weakly enhances Th2 cytokine expression by in vivo polarized Th2 cells. This study on primary human cells demonstrates that basophils and eosinophils are the only direct target leukocytes for IL-33, suggesting that IL-33 promotes allergic inflammation and Th2 polarization mainly by the selective activation of these specialized cells of the innate immune system.

Cross-cultural perspectives on adolescents’ religiosity and family orientation

This chapter explores cultural and individual religious roots of adolescents' family orientation on the basis of multilevel analyses with data from 17 cultural groups. Religion and the family are seen as intertwined social institutions. The family as a source of social support has been identified as an important mediator of the effects of religiosity on adolescent developmental outcomes. The results of the current study show that religiosity was related to different aspects of adolescents' family orientation (traditional family values. value of children, and family future orientation), and that the culture-level effects of religiosity on family orientation were stronger than the individual-level effects. At the cultural level, socioeconomic development added to the effect of religiosity, indicating that societal affluence combined with nonreligious secular orientations is linked to a lower family orientation, especially with regard to traditional family values. The authors suggest that individual religiosity may be of special importance for adolescents' family orientation in contexts where religiosity has lost some significance but religious traditions are still alive and can be (re-)connected to.

Affective Commitment and Job Satisfaction among Non-family Employees: Investigating the Roles of Justice Perceptions and Psychological Ownership

Due to numerous characteristics often attributed to family firms, they constitute a unique context for non-family employees’ justice perceptions. These are linked to non-family employees’ pro-organizational attitudes and behaviors, which are essential for family firms’ success. Even though scholarly interest in non-family employees’ justice perceptions has increased, more research is still needed, also because the mechanism connecting justice perceptions and favorable outcomes is not fully understood yet. We address this gap by explicitly investigating non-family employees’ justice perceptions and by introducing psychological ownership as a mediator in the relationships between justice perceptions (distributive and procedural) and common work attitudes (affective commitment and job satisfaction). Our analysis of a sample of 310 non-family employees from Germany and German-speaking Switzerland reveals that psychological ownership mediates the relationships between distributive justice and affective commitment as well as job satisfaction. This represents valuable contributions to family business research, organizational justice and psychological ownership literature, and to practice.

The Committed and the Happy: Exploring the Effects of Justice and Ownership Perceptions among Non-family Employees

A main challenge that family businesses face is fostering non-family employees' val-ue-creating attitudes, such as affective commitment and job satisfaction. While justice perceptions have been identified as being critical in the creation of these outcomes, the process how they actually evolve is less clear, especially in family firms. We address this gap by introducing psychological ownership as a mediator in the relationships between justice perceptions (distributive and procedural) and common work attitudes (affective commitment and job satisfaction). Our analysis of a sample of 310 non-family employees from family firms in German-speaking Switzerland and Germany reveals that psychological ownership mediates the relationships between distributive justice and affective commitment as well as job satisfaction. This leads to valuable contributions to family business research, organizational justice and psychological ownership literatures, and to practice.

Long-term Success of Family Firms: Investigating Specific Aspects of Firm-level Entrepreneurship and Individual-level Antecedents

Long-term success of family firms is of utmost social and economic importance. Three of its determinants are in the center of this Dissertation: firmlevel entrepreneurial orientation (EO), managers' entrepreneurial behavior, and value-creating attitudes of non-family employees. Each determinant and respective research gaps are addressed by one paper of this cumulative dissertation. Referring to firm-level EO, scholars claim that EO is a main antecedent to firms' both short- and long-term success. However, family firms seem to be successful across generations despite rather low levels of EO. The first paper addresses this paradox by investigating EO patterns of long-lived family firms in three Swiss case studies. The main finding is that the key to success is not to be as entrepreneurially as possible all the time, but to continuously adapt the EO profile depending on internal and external factors. Moreover, the paper suggest new subcategories to different EO dimensions. With regard to entrepreneurial behavior of managers, there is a lack of knowledge how individual-level and organizational level factors affect its evolvement. The second paper addresses this gap by investigating a sample of 403 middle-level managers from both family and non-family firms. It introduces psychological ownership of managers as individual-level antecedent and investigates the interaction with organizational factors. As a central insight, management support is found to strengthen the psychological ownership-entrepreneurial behavior relationship. The third paper is based on the fact that employees' justice perceptions are established antecedents of value-creating employee attitudes such as affective commitment and job satisfaction. Even though family firms are susceptible to nonfamily employees´ perceptions of injustice, corresponding research is scarce. Moreover, the mechanism connecting justice perceptions and positive outcomes is still unclear. Addressing these gaps, the analysis of a sample of 310 non-family employees reveals that psychological ownership is a mediator in the relationships between distributive justice perceptions and both affective commitment and job satisfaction. Altogether, the three papers offer valuable contributions to family business literature with respect to EO, entrepreneurial behavior, and value-creating employee attitudes. Thus, they increase current understanding about important determinants of family firms' long-term success, while opening up numerous ways of future research.