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Title: Biomarkers of acute respiratory allergen exposure: Screening for sensitization potential

Effective hazard screening will require the development of high-throughput or in vitro assays for the identification of potential sensitizers. The goal of this preliminary study was to identify potential biomarkers that differentiate the response to allergens vs non-allergens following an acute exposure in naive individuals. Female BALB/c mice received a single intratracheal aspiration exposure to Metarhizium anisopliae crude antigen (MACA) or bovine serum albumin (BSA) in Hank's Balanced Salt Solution (HBSS) or HBSS alone. Mice were terminated after 1, 3, 6, 12, 18 and 24 h. Bronchoalveolar lavage fluid (BALF) was evaluated to determine total and differential cellularity, total protein concentration and LDH activity. RNA was isolated from lung tissue for microarray analysis and qRT-PCR. MACA administration induced a rapid increase in BALF neutrophils, lymphocytes, eosinophils and total protein compared to BSA or HBSS. Microarray analysis demonstrated differential expression of genes involved in cytokine production, signaling, inflammatory cell recruitment, adhesion and activation in 3 and 12 h MACA-treated samples compared to BSA or HBSS. Further analyses allowed identification of approx 100 candidate biomarker genes. Eleven genes were selected for further assessment by qRT-PCR. Of these, 6 demonstrated persistently increased expression (Ccl17, Ccl22, Ccl7, Cxcl10, Cxcl2, Saa1), while C3ar1 increased frommore » 6-24 h. In conclusion, a single respiratory exposure of mice to an allergenic mold extract induces an inflammatory response which is distinct in phenotype and gene transcription from the response to a control protein. Further validation of these biomarkers with additional allergens and irritants is needed. These biomarkers may facilitate improvements in screening methods.« less
Authors:
 [1] ; ; ; ;  [2]
  1. Curriculum in Toxicology, University of North Carolina-Chapel Hill, CB 7270, Chapel Hill, NC 27599-7270 (United States)
  2. National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, 109 T.W. Alexander Drive, Research Triangle Park, NC 27711 (United States)
Publication Date:
OSTI Identifier:
21344915
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 244; Journal Issue: 2; Other Information: DOI: 10.1016/j.taap.2009.12.027; PII: S0041-008X(09)00534-1; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACUTE EXPOSURE; ALBUMINS; ANTIGENS; ASTHMA; BIOLOGICAL MARKERS; EOSINOPHILS; FUNGI; GENES; HAZARDS; IN VITRO; INFLAMMATION; LUNGS; LYMPHOCYTES; MICE; NEUTROPHILS; RNA; SENSITIZERS; TRANSCRIPTION; VALIDATION ANIMAL CELLS; ANIMALS; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BODY; BODY FLUIDS; CONNECTIVE TISSUE CELLS; DISEASES; LEUKOCYTES; MAMMALS; MATERIALS; NUCLEIC ACIDS; ORGANIC COMPOUNDS; ORGANS; PATHOLOGICAL CHANGES; PLANTS; PROTEINS; REAGENTS; RESPIRATORY SYSTEM; RESPIRATORY SYSTEM DISEASES; RODENTS; SOMATIC CELLS; SYMPTOMS; TESTING; VERTEBRATES