Neutrophils give us a shock

ArticleinThe Journal of clinical investigation 121(4):1260-3 · March 2011with3 Reads
DOI: 10.1172/JCI57296 · Source: PubMed
Systemic anaphylaxis is generally recognized as a severe allergic reaction caused by IgE-mediated activation of mast cells, leading to massive release of vasoactive mediators that induce acute hypotension and shock. However, experimental evidence in mice suggests that this view is too simple. Using a variety of techniques to manipulate immune cell makeup, Jönsson et al. come to the conclusion in this issue of the JCI that recognition of IgG1 and IgG2 antibodies by FcγRIII and FcγRIV receptors on neutrophils is a major pathway for induction of anaphylaxis. These exciting results suggest that we have to reevaluate our models for anaphylaxis in humans, which will have a direct impact on our therapeutic approaches for prevention of this potential deadly hypersensitivity reaction.
  • [Show abstract] [Hide abstract] ABSTRACT: Impressive advances in defining the properties of receptors for the Fc portion of immunoglobulins (FcR) have been made over the past several years. Ligand specificities were systematically analyzed for both human and mouse FcRs that revealed novel receptors for specific IgG subclasses. Expression patterns were redefined using novel specific anti-FcR mAbs that revealed major differences between human and mouse systems. The in vivo roles of IgG receptors have been addressed using specific FcR knockout mice or in mice expressing a single FcR, and have demonstrated a predominant contribution of mouse activating IgG receptors FcγRIII and FcγRIV to models of autoimmunity (eg, arthritis) and allergy (eg, anaphylaxis). Novel blocking mAbs specific for these activating IgG receptors have enabled, for the first time, the investigation of their roles in vivo in wild-type mice. In parallel, the in vivo properties of human FcRs have been reported using transgenic mice and models of inflammatory and allergic reactions, in particular those of human activating IgG receptor FcγRIIA (CD32A). Importantly, these studies led to the identification of specific cell populations responsible for the induction of various inflammatory diseases and have revealed, in particular, the unexpected contribution of neutrophils and monocytes to the induction of anaphylactic shock.
    Article · Apr 2012
  • [Show abstract] [Hide abstract] ABSTRACT: Food allergy is a growing health problem with serious concerns due to high potential for fatality. Rapid advances in the knowledge on causes and mechanisms as well as in developing effective prevention/therapeutic strategies are needed. To meet these goals, mouse models that simulate the human disorder are highly desirable. During the past decade, several mouse models of food allergies have been reported. Here we briefly reviewed the human disorder and then critically evaluated these models seeking answers to the following important questions: To what extent do they simulate the human disorder? What are the strengths and limitations of these models? What are the challenges facing this scientific area? Our analysis suggest that: (i) the mouse models, with inherent strengths and limitations, are available for many major food allergies; there is scope for additional model development and validation; (ii) models mostly simulate the severe forms of human disorder with similar immune and clinical features; (iii) the approaches used to develop some of the mouse models may be questionable; and (iv) the specific mechanisms of sensitization as wells as oral elicitation of fatal reactions in both humans and mice remains incompletely understood and therefore warrants further research.
    Article · Jan 2013

Recommended publications

Discover more