Pathological inflammation and autoimmune disease frequently involve elevated neutrophil activity in the absence of infectious agents. Tumor necrosis factor-α (TNF-α) contributes to many of the problems associated with autoimmune diseases. We investigated the ability of serum α-1 antitrypsin (AAT) to control TNF-α biosynthesis and signaling in neutrophils and assessed whether AAT deficiency (AATD) is a TNF-α-related disease. In vitro studies demonstrate that serum AAT coordinates TNF-α intracellular signaling and neutrophil degranulation of tertiary and secondary granules via modulation of ligand-receptor interactions. AATD patients homozygous for the Z allele were characterized by increased activation of the TNF-α system, as demonstrated by increased membrane TNF-α levels and increased plasma concentrations of TNF receptor 1 and neutrophil-released secondary and tertiary granule proteins. The incidence of autoantibodies directed against degranulated lactoferrin and surface protein accessible to these antibodies was increased in ZZ-AATD, leading to an enhanced rate of neutrophil reactive oxygen species production. Treatment of ZZ-AATD individuals with AAT augmentation therapy resulted in decreased membrane TNF-α expression and plasma levels of granule antigenic proteins and immunoglobulin G class autoantibodies. These results provide a mechanism by which AAT augmentation therapy affects TNF-α signaling in the circulating neutrophil, indicating promising potential of this therapy for other TNF-α-related diseases.
In an experimental study, we investigate perceived relative power in negotiations and its effect on the distribution of resources and the integrativeness of agreements. We contrast perceived relative power with the objective individual level measure of power often used in past research: the parties' alternatives to a negotiated agreement. We found that alternatives affected the distribution of outcomes, while perceived relative power and alternatives affected the integrativeness of outcomes. We found that negotiating pairs who perceived a smaller difference in relative power reached agreements of greater integrativeness than pairs who perceived a greater power difference, even after controlling for alternatives and aspirations. We explore the implications of treating power in negotiations as a perceived and relational construct.
The Publisher regrets that an error occurred in the name of the 6th listed co-author for this paper. B. Matthias was listed in the original paper instead of M. Borchert; the correct listing can be seen above.
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