Antigenic changes in human albumin caused by reactivity with the occupational allergen diphenylmethane diisocyanate
Section snippets
Chemicals and reagents
Low endotoxin certified human albumin was obtained from Sigma Chemical (St. Louis, MO, USA), 4′4-diphenyl methane diisocyanate was obtained from Aldrich (St. Louis, MO, USA), and acetone was obtained from J.T. Baker (Phillipsburg, NJ, USA).
Reactivity of MDI with human albumin
Human albumin was solubilized in phosphate-buffered saline (PBS: 20 mM phosphate and 140 mM NaCl, pH 7.2) at 0.5% (w/v) to achieve a concentration (∼74 μM) similar to human airway epithelial lining fluid [17]. A 50% (w/v) stock solution of MDI in acetone was
Effects of MDI exposure on human albumin
A rapid reaction (X + Y → Z) occurs when human albumin (X) is mixed with diisocyanate (Y), a class of chemicals known to cause asthma. The products of this reaction (Z) are antigenic to the human immune system but remain incompletely understood. We characterized the different reaction products between 4,4′-MDI and human albumin that result when a range of different starting reactant concentrations are present under the biologically relevant reaction conditions (see Materials and methods). Human
Discussion
This article has provided new insight into the antigenic changes that occur in the self protein, human albumin, when exposed to the occupational allergen MDI. Advances were made possible by combining several different analytical methods to characterize the range of MDI–albumin reaction products that form under different exposure conditions. Biologically relevant MDI–albumin reaction products produced in vitro were identified by serum IgG from MDI-exposed workers and further characterized
Acknowledgments
We thank the Yale Keck Center for its assistance with the HPLC and MS studies. We are especially thankful to Tom Abbott, Mary LoPresti, Kathy Stone, and Walt McMurray for their helpful guidance and data analysis. Funding was provided by the National Institute of Environmental Health and Safety through Grants R42-ES016728 and R41-ES018021 (to A.V.W.) and by the National Institute of Occupational Health and Safety (to C.A.R.).
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