Cell and molecular biology of chemical allergy.
OBJECTIVE
The objective of this review is to provide current approaches to gain increased understanding of the molecular basis of chemical allergenicity. Chemical allergy refers to an allergic reaction to a low molecular weight agent (ie, <1 kD). The symptoms and pathology of chemical asthma resemble those of allergy to larger sized agents, such as pollens, weeds, and danders. The differences relate to mechanisms of disease. To stimulate an immune response, low molecular weight chemicals function as haptens and bind to carrier macromolecules. This article focuses on the chemical reactions and physicochemical characteristics of chemical allergens.


METHODS
Data were obtained from published clinical reports and from the Documentation of Threshold Limit Values (1998) published by the American Congress of Governmental Industrial Hygienists.


RESULTS
In vitro studies indicate the stoichiometric reaction of some chemical allergens with glutathione and the subsequent transfer of the allergen from glutathione to other nucleophiles. Computer-generated structure-activity relationship models have been developed for chemicals that induce respiratory allergy. The models, based on physicochemical properties of the agents, have high sensitivity and specificity.


CONCLUSIONS
The structure-activity relationship model suggests that chemical binding is the essential feature of chemical allergens. Their in vivo reactions with thiols may result in glutathione deficiency with consequent alteration in cellular reduction-oxidation (redox) status, release of cytokines, and promotion of the T helper cell 2 phenotype. Prevention of permanent disease is dependent on periodic medical surveillance of affected workers. When detected early, the disease can frequently be reversed.
Karol
M H
MH
Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pennsylvania, USA. mhk+@pitt.edu
Macina
O T
OT
Cunningham
A
A
D000485:Allergens / Q000009:adverse effects* / Q000737:chemistry*; D001249:Asthma / Q000139:chemically induced* / Q000503:physiopathology; D002468:Cell Physiological Phenomena; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology* / Q000503:physiopathology; D007287:Inorganic Chemicals / Q000009:adverse effects* / Q000737:chemistry; D008967:Molecular Biology; D009930:Organic Chemicals / Q000009:adverse effects* / Q000737:chemistry
D000485:Allergens; D007287:Inorganic Chemicals; D009930:Organic Chemicals