Babu Gonipeta1, Radhakrishna Para1, Yingli He1, Ines Srkalovic1, Tina Ortiz1, Eunjung Kim2, Sitaram Parvataneni1, Venu Gangur3. 1. Food Allergy and Immunology Laboratory, Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 United States of America. 2. Food Allergy and Immunology Laboratory, Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 United States of America; Division of Applied Life Science (BK 21 Program), Gyeongsang National University, Jinju, South Korea. 3. Food Allergy and Immunology Laboratory, Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 United States of America. Electronic address: gangur@msu.edu.
Abstract
BACKGROUND: Nut allergy is a growing and potentially fatal public health problem. We have previously reported a novel mouse model of near-fatal hazelnut (HN) allergy that involves transdermal sensitization followed by oral elicitation of allergic reactions. Here we studied the cardiac mast cell and cardiac tissue responses during oral nut induced allergic reaction in this mouse model. METHODS: Groups of mice were sensitized with HN and specific and total IgE were measured by ELISA. Oral allergic reaction was quantified by rectal thermometry and plasma mouse mast cell protease (mMCP)-1 by ELISA. Cardiovascular functions were determined by a non-invasive tail cuff method. Mucosal mast cells (MMC) and intestinal connective tissue MC (CTMC) were studied by immunohistochemistry (IHC) for mMCP-1 and mMCP-4 protein expression respectively. Cardiac MC were studied by toluidine blue (TB) as well as by the above IHC methods. Cytokines and chemokines in the tissues were quantified by a multiplex protein array method. RESULTS: Oral allergen challenge (OAC) of transdermal sensitized mice results in hypothermia, hypotension, tachycardia and rapid elevation of circulating mMCP-1. The IHC analysis of small intestine found significant expansion of mMCP-1+ MMCs and mMCP-4+ CTMCs. The TB analysis of cardiac tissues showed degranulation of majority of cardiac MCs. The IHC analysis of cardiac tissues showed very little mMCP-1 expression, but marked mMCP-4 expression. Furthermore, repeated OAC resulted in significant expansion of mMCP-4+ cardiac MCs in both the pericardium and the myocardium. Protein array analysis revealed significant elevation of cardiac IL-6 and CCR1/3 and CXCR2 signaling chemokines upon oral elicitation compared to sensitization alone. CONCLUSION: These results demonstrate that: (i) besides the intestine, cardiac mast cells and the cardiac tissue respond during oral nut induced allergic reaction; and (ii) repeated oral elicitation of reaction is associated with cardiac mMCP-4+ mast cell expansion and elevation of cardiac IL-6, and CCR1/3 and CXCR2 signaling chemokines.
BACKGROUND:Nutallergy is a growing and potentially fatal public health problem. We have previously reported a novel mouse model of near-fatal hazelnut (HN) allergy that involves transdermal sensitization followed by oral elicitation of allergic reactions. Here we studied the cardiac mast cell and cardiac tissue responses during oral nut induced allergic reaction in this mouse model. METHODS: Groups of mice were sensitized with HN and specific and total IgE were measured by ELISA. Oral allergic reaction was quantified by rectal thermometry and plasma mouse mast cell protease (mMCP)-1 by ELISA. Cardiovascular functions were determined by a non-invasive tail cuff method. Mucosal mast cells (MMC) and intestinal connective tissue MC (CTMC) were studied by immunohistochemistry (IHC) for mMCP-1 and mMCP-4 protein expression respectively. Cardiac MC were studied by toluidine blue (TB) as well as by the above IHC methods. Cytokines and chemokines in the tissues were quantified by a multiplex protein array method. RESULTS: Oral allergen challenge (OAC) of transdermal sensitized mice results in hypothermia, hypotension, tachycardia and rapid elevation of circulating mMCP-1. The IHC analysis of small intestine found significant expansion of mMCP-1+ MMCs and mMCP-4+ CTMCs. The TB analysis of cardiac tissues showed degranulation of majority of cardiac MCs. The IHC analysis of cardiac tissues showed very little mMCP-1 expression, but marked mMCP-4 expression. Furthermore, repeated OAC resulted in significant expansion of mMCP-4+ cardiac MCs in both the pericardium and the myocardium. Protein array analysis revealed significant elevation of cardiac IL-6 and CCR1/3 and CXCR2 signaling chemokines upon oral elicitation compared to sensitization alone. CONCLUSION: These results demonstrate that: (i) besides the intestine, cardiac mast cells and the cardiac tissue respond during oral nut induced allergic reaction; and (ii) repeated oral elicitation of reaction is associated with cardiac mMCP-4+ mast cell expansion and elevation of cardiac IL-6, and CCR1/3 and CXCR2 signaling chemokines.
Authors: Rick Jorgensen; Rajsri Raghunath; Haoran Gao; Eric Olson; Perry K W Ng; Venu Gangur Journal: Int J Mol Sci Date: 2022-06-10 Impact factor: 6.208