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Characterization of a Mouse Model of Allergy to a Major Occupational Latex Glove Allergen Hev b 5

Characterization of a Mouse Model of Allergy to a Major Occupational Latex Glove Allergen Hev b 5,Charles L. Hardy,Linda Kenins,Alexander C. Drew,Jenn

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Characterization of a Mouse Model of Allergy to a Major Occupational Latex Glove Allergen Hev b 5   (Citations: 4)
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Allergen-specific immunotherapy is a clinically proven effective treat- allergen. In excess of 50% of latex allergic subjects expresses ment for many allergic diseases, including asthma; however, it is the asthma phenotype, with latex emerging as a major cause not currently available for latex allergy because of the high risk of of occupational asthma. It has been reported that exposure to anaphylaxis. There is, therefore, a crucial need for an animal model of Hevea brasiliensis may induce occupational asthma in 6% of latex allergy in which to develop effective immunotherapy. Previous exposed individuals (11). mouse models of latex allergy either did not characterize the allergic Previous mouse models of latex allergy that used unfraction- pulmonary immune response or used crude latex extracts, making ated latex extracts (12-16), although showing allergic Th2-type it difficult to quantify the contribution of individual proteins and immune responses, were unable to define the role of individual limiting their usefulness for developing specific immunotherapy. We allergens. In another model, mice immunized with a recombi- immunized mice with recombinant Hev b 5, a defined major latex nant Hev b 5 (rHev b 5)-maltose binding protein fusion protein allergen, or latex glove protein extract, representing the range of mounted specific IgE and IgG responses and permitted identi- occupationally encountered processed latex allergens. The immune fication of T- and B-cell epitopes (17, 18). However, other response was compared with that seen in ovalbumin-immunized parameters of an allergic response, including eosinophilic in- mice. Immunization with Hev b 5 or glove extract elicits hallmarks flammation of the lung and mucus hypersecretion, were not of allergic pulmonary Th2-type immune responses, comparable to demonstrated. those for ovalbumin, including (1) serum antigen-specific IgE, (2) We have used purified rHev b 5 lacking maltose binding an eosinophilic inflammatory infiltrate in the lung, (3) increased protein (19) to develop a mouse model of allergy to Hev b 5 interleukin-5 in lung bronchoalveolar lavage fluid, and (4) mucus and have characterized the allergic immune response. Mice hypersecretion by epithelial cells in the lung airways. This mouse rendered allergic to ovalbumin (OVA) have been widely stud- model will aid the development of potentially curative treatments ied and serve as a prototypic standard against which other for latex-sensitized individuals, including those with occupational mouse allergy models may be evaluated. We immunized mice asthma. seen in the well-characterized OVA asthma model. Addition- ally, mice were immunized with glove extract (GE) to validate Latex allergy is an important medical problem, particularly the Hev b 5 model using a clinically relevant sensitizing allergen among healthcare workers and patients with spina bifida. The extract. Immunization with Hev b 5 or GE elicits key hall- allergic reaction to latex ranges from urticaria, conjunctivitis, marks of an allergic Th2-type immune response, including (1) and rhinitis to asthma, anaphylactic shock, and occasionally a predominantly eosinophilic inflammatory infiltrate in the death (1, 2). Exposure occurs by cutaneous, mucosal, and paren- bronchoalveolar lavage (BAL) and lung tissue, (2) serum Hev teral routes, with aerosol inhalation and degree of exposure to b 5- and GE-specific IgE, and (3) a significant increase in latex allergens playing important roles in the development of mucus-producing cells in the lung airways. allergy (3, 4). Allergen-specific immunotherapy is a clinically proven effective treatment for a variety of allergic diseases; METHODS however, it is not currently available for latex allergy because of the high risk of anaphylaxis (5, 6). There is, therefore, an Mice urgent need for animal models of latex allergy in which to Female BALB/c mice aged 7-8 weeks were obtained from Monash Univer- develop effective allergen-specific immunotherapy, as a prelude sity Animal Services (Clayton, Melbourne, Australia) or the Walter and to clinical studies.
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