These studies are designed to investigate the pathophysiology of the inflammatory response to intrabronchial allergen challenge in asthmatic subjects. These inflammatory responses are expressed clinically as the late asthmatic response (LAR). Initially we will investigate the hypothesis that the LAR develops as a result of quantitative or qualitative differences in mediators released at the time of the immediate response to allergen challenge. In parallel, we will investigate the alternative hypotheses that inflammatory cells from late responders have either a hyperreactive response to pro-inflammatory mediators or that they fail to down- regulate properly in response to inhibitory stimuli. A third possibility is that it is the ability of alveolar macrophages to be triggered to secrete mediators in response to allergen which results in the selective development of a LAR. We will investigate the ability of macrophages to secrete IL-1 and TNF in an IgE- dependent fashion. This will allow us to distinguish whether mast cells or macrophaphages are responsible for the LAR, based on our ability to identify the mast cell-specific product histamine as opposed to the macrophage-specific products IL-1 or TNF. Finally, we will perform a controlled trial of immunotherapy in patients with extrinsic asthma. These latter studies are designed to prospectively investigate the pathophysiological basis by which a successful course of immunotherapy abrogates the LAR to challenge with allergen.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Specialized Center (P50)
Project #
5P50AI024848-05
Application #
3803530
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1991
Total Cost
Indirect Cost
Name
National Jewish Health
Department
Type
DUNS #
City
Denver
State
CO
Country
United States
Zip Code
80206
Xiang, Shi-Hua; Finzi, Andrés; Pacheco, Beatriz et al. (2010) A V3 loop-dependent gp120 element disrupted by CD4 binding stabilizes the human immunodeficiency virus envelope glycoprotein trimer. J Virol 84:3147-61
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