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Pathogenesis and management of anaphylaxis: Current status and future challenges

Journal of Allergy and Clinical Immunology (Impact Factor: 11.25). 04/2005; 115(3):571-4. DOI: 10.1016/j.jaci.2004.12.1133
Source: PubMed
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    ABSTRACT: Anaphylaxis is an acute, severe, and potentially fatal systemic allergic reaction. Immunoglobulin E (IgE), mast cells, and histamine have long been associated with anaphylaxis, but an alternative pathway mediated by IgG has been suggested to be more important in the elicitation of anaphylaxis. Here, we showed that basophils, the least common blood cells, were dispensable for IgE-mediated anaphylaxis but played a critical role in IgG-mediated, passive and active systemic anaphylaxis in mice. In vivo depletion of basophils but not macrophages, neutrophils, or NK cells ameliorated IgG-mediated passive anaphylaxis and rescued mice from death in active anaphylaxis. Upon capture of IgG-allergen complexes, basophils released platelet-activating factor (PAF), leading to increased vascular permeability. These results highlight a pivotal role for basophils in vivo and contrast two major, distinct pathways leading to allergen-induced systemic anaphylaxis: one mediated by basophils, IgG, and PAF and the other "classical" pathway mediated by mast cells, IgE, and histamine.
    Immunity 05/2008; 28(4):581-9. DOI:10.1016/j.immuni.2008.02.008 · 19.75 Impact Factor
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    ABSTRACT: Basophils circulate in the peripheral blood under physiological conditions, and they are recruited to affected tissues in allergic reactions, albeit in small numbers. Because of their rarity (less than 1% of peripheral blood leukocytes are basophils), and their similarity to mast cells, basophils have often been considered the lesser relatives of mast cells. Moreover, because basophils have been so difficult to identify, mice were erroneously believed for a long time to lack them. Therefore, the assumption that basophils have only redundant roles has remained unquestioned until recently. The flow-cytometric identification of basophils in mice and the development of in vivo models and reagents useful for their functional analyses have greatly advanced the field of basophil research. Previously unrecognized roles of basophils, dis-tinct from those of mast cells, have been shown in allergic responses and the regulation of acquired immunity. In this re-view, we mainly focus on roles of basophils in immediate-and delayed-onset allergic reactions. Basophils are crucial ini-tiators, rather than effectors, in the development of IgE-mediated, chronic cutaneous allergic inflammation, which is char-acterized by the massive infiltration of eosinophils and neutrophils and can be elicited even in the absence of mast cells and T cells. Basophils are dispensable for the induction of IgE-mediated systemic anaphylaxis, unlike mast cells, but play a major role in IgG-mediated passive and active systemic anaphylaxis, through the release of platelet-activating factor in response to stimulation with antigen-IgG immune complexes. Thus, basophils and their products appear to be promising therapeutic targets for allergic disorders.
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    ABSTRACT: The term anaphylaxis is used to describe both IgE, immune-mediated reactions and non- allergic, non-immunologically triggered events. Co-morbities such as asthma or infection, exercise, alcohol or stress and concurrent medications such as beta-blockers, angiotensin converting-enzyme inhibitors (ACEI) and aspirin increase the risk of anaphylaxis occurring. The pathophysiology involves activated mast cells and basophils releasing preformed, granule-associated mediators, and newly formed lipid mediators, as well as generating cytokines and chemokines. These cause vasodilatation, increased capillary permeability and smooth muscle contraction, and attract new cells to the area. Positive feedback mechanisms amplify the reaction, although conversely reactions can self-limit. Parenteral penicillin, hymenopteran stings and foods are the most common causes of IgE, immune-mediated fatalities, with radiocontrast media, aspirin and other non-steroidal anti-inflammatory drugs most commonly responsible for non-allergic fatalities. Deaths are rare but do occur by hypoxia from upper airway asphyxia or severe bronchospasm, or by profound shock from vasodilatation and extravascular fluid shift. Oxygen, adrenaline (epinephrine) and fluids are first-line treatment. Adrenaline (epinephrine) 0.01 mg/kg to a maximum of 0.5 mg (0.5 mL of 1:1000 adrenaline) i.m. in the upper lateral thigh acts to reverse all the features of anaphylaxis, as well as inhibiting further mediator release. Crystalloids such as normal saline or Hartmann's solution at 10-20 mL/kg are essential in shock. The role of H1 and H2 antihistamines, steroids and glucagon is unclear. They should only be considered once cardiovascular stability has been achieved with first-line agents. Discharge may follow observation from four to six hours after full recovery. A clear discharge plan, and referral to an allergist for all significant, recurrent, unavoidable or unknown stimulus reactions are essential. Patient education is important to successful, long-term care. (Emergencias 2009;21:213-223)