title: Cardiac mMCP-4+ mast cell expansion and elevation of IL-6, and CCR1/3 and CXCR2 signaling chemokines in an adjuvant-free mouse model of tree nut allergy.
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.
  
  
  CONCLUSIONS
  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.affiliation: Food Allergy and Immunology Laboratory, Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 United States of America.
authors.forename: Babu
authors.initials: B
authors.lastname: Gonipeta
authors.affiliation: Food Allergy and Immunology Laboratory, Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 United States of America.
authors.forename: Radhakrishna
authors.initials: R
authors.lastname: Para
authors.affiliation: Food Allergy and Immunology Laboratory, Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 United States of America.
authors.forename: Yingli
authors.initials: Y
authors.lastname: He
authors.affiliation: Food Allergy and Immunology Laboratory, Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 United States of America.
authors.forename: Ines
authors.initials: I
authors.lastname: Srkalovic
authors.affiliation: Food Allergy and Immunology Laboratory, Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 United States of America.
authors.forename: Tina
authors.initials: T
authors.lastname: Ortiz
authors.affiliation: 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.
authors.forename: Eunjung
authors.initials: E
authors.lastname: Kim
authors.affiliation: Food Allergy and Immunology Laboratory, Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 United States of America.
authors.forename: Sitaram
authors.initials: S
authors.lastname: Parvataneni
authors.affiliation: 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.
authors.forename: Venu
authors.initials: V
authors.lastname: Gangur
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D018932:Chemokine CCL2 / Q000097:blood; D031211:Corylus / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D021184:Nut Hypersensitivity / Q000276:immunology*; D054389:Receptors, CCR1 / Q000235:genetics / Q000378:metabolism*; D054397:Receptors, CCR3 / Q000235:genetics / Q000378:metabolism*; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D000485:Allergens; C491768:Ccl2 protein, mouse; C515301:Ccr1 protein, mouse; C515351:Ccr3 protein, mouse; D018932:Chemokine CCL2; D015850:Interleukin-6; D054389:Receptors, CCR1; D054397:Receptors, CCR3; D023063:Receptors, Interleukin-8B; D007073:Immunoglobulin E; D012697:Serine Endopeptidases; C066932:mast cell protease 4
keywords: Cardiac mast cell; Chemokines; Cytokines; Hazelnut allergy; Intestinal mast cell; Mouse model