Scavenger Receptors and Resistance to Inhaled Allergens

Abstract

Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE 01-02-20072. REPORT TYPE Annual DATES COVERED SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTESOriginal contains colored plates: ALL DTIC reproductions will be in black and white. ABSTRACTAfter OVA sensitization and aerosol challenge, SR-AI/II and MARCO-deficient mice exhibited greater eosinophilic airway inflammation and airway hyperresponsiveness compared to wild-type mice. A role for simple SRA-mediated antigen clearance ('scavenging') by lung macrophages was excluded by observation of comparable uptake of fluorescent OVA by wild-type and SRA-deficient lung MΦs and DCs. In contrast, airway instillation of fluorescent antigen revealed significantly higher traffic of labelled DCs to thoracic lymph nodes in SRA-deficient mice than in controls. The increased migration of SRA-deficient DCs was accompanied by enhanced proliferation in thoracic lymph nodes of adoptively transferred OVA-specific T cells after airway OVA challenge. The data identify a novel role for SRAs expressed on lung DCs in down-regulation of specific immune responses to aero-allergens by reduction of DC migration from the site of antigen uptake to the draining lymph nodes. References……………………………………………………………………………. 5 SUBJECT TERMSAppendices…………………………………………………………………………… 5 4 INTRODUCTION: Narrative that briefly (one paragraph) describes the subject, purpose and scope of the research.Our central hypothesis is 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 is to determine whether 1) decreased levels of SRAs (mediated by environmental stresses) increase susceptibility to asthma or pneumonia; and 2) therapy to increase or maintain normal levels of scavenger receptors will increase resistance to asthma and pneumonia. The scope of the research includes studies using in vivo mouse models (Aim 1), studies of the specific role of alveolar macrophages (Aim 2) and dendritic cells (Aim 3) and studies of the effec...

The Protein Corona of Plant Virus Nanoparticles Influences their Dispersion Properties, Cellular Interactions, and In Vivo Fates

“…[ 53,54 ] However, the accumulation of carbon nanotubes in the lungs can be prevented by shielding with longer PEG chains ( M W = 2000-5400 Da), [ 55 ] suggesting that the accumulation of VNPs in the lungs refl ects their aggregation and fi ltration through lung capillaries or uptake by lung macrophages that are known to scavenge for and internalize foreign macromolecules. [ 56 ] This theory is supported by the fact that the aggregation of GPRPP particles happens almost instantaneously (within a minute) after their introduction in plasma (as observed in vitro, Figure 5 A) and the lungs with a high density of capillary vasculature are the central organ for capture of aggregated particulates.…”