ovalbumin and Shock

Severe IgE-mediated, food-induced anaphylactic reactions are characterized by pulmonary venous vasodilatation and fluid extravasation, which are thought to lead to the life-threatening anaphylactic phenotype. The underlying immunologic and cellular processes involved in driving fluid extravasation and the severe anaphylactic phenotype are not fully elucidated.. We sought to define the interaction and requirement of IL-4 and vascular endothelial (VE) IL-4 receptor α chain (IL-4Rα) signaling in histamine-abelson murine leukemia viral oncogene homology 1 (ABL1)-mediated VE dysfunction and fluid extravasation in the severity of IgE-mediated anaphylactic reactions in mice.. Mice deficient in VE IL-4Rα and models of passive and active oral antigen- and IgE-induced anaphylaxis were used to define the requirements of the VE IL-4Rα and ABL1 pathway in severe anaphylactic reactions. The human VE cell line (EA.hy926 cells) and pharmacologic (imatinib) and genetic (short hairpin RNA knockdown of IL4RA and ABL1) approaches were used to define the requirement of this pathway in VE barrier dysfunction.. IL-4 exacerbation of histamine-induced hypovolemic shock in mice was dependent on VE expression of IL-4Rα. IL-4- and histamine-induced ABL1 activation in human VE cells and VE barrier dysfunction was ABL1-dependent. Development of severe IgE-mediated hypovolemia and shock required VE-restricted ABL1 expression. Treatment of mice with a history of food-induced anaphylaxis with the ABL kinase inhibitor imatinib protected the mice from severe IgE-mediated anaphylaxis.. IL-4 amplifies IgE- and histamine-induced VE dysfunction, fluid extravasation, and the severity of anaphylaxis through a VE IL-4Rα/ABL1-dependent mechanism. These studies implicate an important contribution by the VE compartment in the severity of anaphylaxis and identify a new pathway for therapeutic intervention of IgE-mediated reactions.

Topics: Allergens; Anaphylaxis; Animals; Antibodies; Cell Line; Endothelium, Vascular; Female; Histamine; Humans; Imatinib Mesylate; Immunoglobulin E; Interleukin-4; Male; Mice, Inbred BALB C; Mice, Transgenic; Ovalbumin; Proto-Oncogene Proteins c-abl; Receptors, Interleukin-4; Shock

Topics: Anaphylaxis; Animals; Female; Guinea Pigs; Haptens; Hemoglobins; Histamine; Histamine H1 Antagonists; Hyperkalemia; Isotonic Solutions; Male; Ovalbumin; Potassium; Potassium Chloride; Shock; Sodium Chloride

Topics: Anaphylaxis; Animals; Blood Chemical Analysis; Catecholamines; Chlorprothixene; Epinephrine; Lagomorpha; Muramidase; Nialamide; Norepinephrine; Ovalbumin; Prednisone; Rabbits; Research; Serotonin; Shock

Topics: Animals; Leukocytes; Ovalbumin; Rats; Shock