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Cellular and Immunohistochemical Changes in Anaphylactic Shock Induced in the Ovalbumin-Sensitized Wistar Rat Model.

ABSTRACT: Anaphylactic shock (AS) is a life-threatening, multisystem disorder arising from sudden release of mast cell- and basophil-derived mediators into the circulation. In this study, we have used a Wistar rat model to investigate AS-associated histopathologic changes in various organs. Rats were sensitized with ovalbumin (1 mg s.c), and AS was induced by intravenous injection of ovalbumin (1 mg). Experimental groups included nonallergic rats (n = 6) and allergic rats (n = 6). Heart rate and blood pressure were monitored during one hour. Organs were harvested at the end of the experiment and prepared for histologic and immunohistochemical studies. Lung, small bowel mucosa and spleen were found to undergo heavy infiltration by mast cells and eosinophils, with less prominent mast cell infiltration of cardiac tissue. The mast cells in lung, small bowel and spleen exhibited increased expression of tryptase, c-kit and induced nitric oxide synthase (iNOS). Increased expression of endothelial nitric oxide synthase (eNOS) by vascular endothelial cells was noted principally in lung, heart and small bowel wall. The Wistar rat model of AS exhibited accumulation of mast cells and eosinophils in the lung, small bowel, and spleen to a greater extent than in the heart. We conclude that lung and gut are principal inflammatory targets in AS, and likely contribute to the severe hypotension of AS. Targeting nitric oxide (NO) production may help reduce AS mortality.

SUBMITTER: Al-Salam S

PROVIDER: S-EPMC6468713 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Cellular and Immunohistochemical Changes in Anaphylactic Shock Induced in the Ovalbumin-Sensitized Wistar Rat Model.

Al-Salam Suhail S Aburawi Elhadi H EH Al-Hammadi Suleiman S Dhanasekaran Sekhar S Shafiuallah Mohamed M Yasin Javed J Sudhadevi Manjusha M Awwad Aktham A Alper Seth L SL Kazzam Elsadig E EE Bellou Abdelouahab A

Biomolecules 20190313 3

Anaphylactic shock (AS) is a life-threatening, multisystem disorder arising from sudden release of mast cell- and basophil-derived mediators into the circulation. In this study, we have used a Wistar rat model to investigate AS-associated histopathologic changes in various organs. Rats were sensitized with ovalbumin (1 mg s.c), and AS was induced by intravenous injection of ovalbumin (1 mg). Experimental groups included nonallergic rats (n = 6) and allergic rats (n = 6). Heart rate and blood pre ...[more]

PMID: 30871269

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Project description:Allergy is a major public health concern, the main treatment for which is symptomatic relief with anti-inflammatory drugs. A key clinical challenge is to induce specific tolerance in order to control allergen-specific memory B and T cells, and specifically block effector cell responses. Our lab recently developed antigen-specific regulatory T-cell (Treg) therapies as a treatment for adverse responses. Recently, we created a chimeric antigen receptor (CAR) approach in which we engineered a target protein antigen, ovalbumin (OVA), linked with the transmembrane and signal transduction domains, CD28-CD3? to directly target B cells and sensitized mast cells in an allergy model. We named this receptor "BAR" for B-cell Antibody Receptor. Murine or human Tregs, transduced with a BAR containing OVA or control Tregs expressing an unrelated antigen, were successfully expanded in vitro and tested in the murine OVA-alum allergy model with measurable titers of anti-OVA IgE. Because BAR Tregs express the target antigen and could interact with specific IgE on sensitized mast cells, we first demonstrated that intravenously injected OVA-BAR Tregs did not directly lead to a drop in temperature or release of mediators in plasma indicative of anaphylaxis. Forty-eight hours later, mice were challenged intraperitoneally with 200??g OVA to induce an anaphylactic reaction, and temperature immediately measured for 30?min. We found that OVA-BAR Tregs protected mice from hypothermia, whereas mice given control BARs (expressing an unrelated antigen) or PBS showed substantial temperature drops indicative of anaphylaxis when systemically challenged with OVA. Importantly, this effect was also demonstrated in a passive anaphylaxis model in which mice that received anti-OVA IgE antibody were protected from hypothermia when treated with OVA-BAR Tregs prior to systemic OVA challenge. These results provide proof of principle that engineered allergen-specific T-regulatory cells can provide clinical protection against severe allergic reactions in individuals already IgE-sensitized to an allergen.

Dataset Information

Cellular and Immunohistochemical Changes in Anaphylactic Shock Induced in the Ovalbumin-Sensitized Wistar Rat Model.

Publications

Cellular and Immunohistochemical Changes in Anaphylactic Shock Induced in the Ovalbumin-Sensitized Wistar Rat Model.

Similar Datasets

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