Scavenger Receptors and Resistance to Inhaled Allergens
Final rept. 17 Jan 2006-16 Jan 2010
HARVARD SCHOOL OF PUBLIC HEALTH BOSTON MA
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Our central hypothesis was that lung macrophage scavenger receptors normally function to bind and clear inhaled allergens and pathogens, thereby preventing allergic responses and infections. The purpose of the project was to determine whether 1 decreased levels of SRAs mediated by environmental stresses increase susceptibility to asthma and 2 modulating levels of scavenger receptors will affect resistance to asthma. The results indicate that scavenger receptors modulate the allergic response, primarily by modifying dendritic cell trafficking to thoracic lymph nodes in the setting of asthma. Dendritic cells deficient in the scavenger receptors SRA III or MARCO traveled to the lymph nodes faster, and generated a more robust asthmatic response when allergen was delivered into the lungs. Scavenger receptors are linked to oxidant air pollution responses in a complex manner. Oxidant air pollution increases expression of MARCO which serves to scavenge oxidized pro-inflammatory lipids, thereby dampening, but not eradicating, acute inflammatory responses.
- Medicine and Medical Research