Accession Number:

AD1047444

Title:

The Role of Alveolar Macrophage Beta-2 Adrenergic Receptors in Acute Lung Injury

Descriptive Note:

Technical Report,30 Sep 2016,29 Sep 2017

Corporate Author:

The University of Chicago Chicago United States

Personal Author(s):

Report Date:

2017-10-01

Pagination or Media Count:

15.0

Abstract:

The overall goal of this project is to understand how beta2AR signaling in macrophages contributes to Acute Respiratory Distress Syndrome, which is a significant contributor to morbidity and mortality in military and civilian settings. To achieve this goal, we proposed three specific aims. In Aim 1, we proposed to determine whether beta2-agonists worsen influenza A-induced lung injury via beta2ARs on tissue-resident andor monocyte-derived alveolar macrophages. In Aim 2, we aimed to investigate whether IL-6 andor recruitment of monocyte derived macrophages are required for the effects of 2ARs activation on influenza A-induced lung injury. In Aim 3, we proposed to determine whether inhibition of beta2ARs attenuates age-related worsening of influenza A-induced acute lung injury. In this reporting period, we confirmed that beta2ARs on monocytes and macrophages are critical for influenza A virus-induced acute lung injury. We developed and validated a method to clearly identify tissue resident and monocyte-derived macrophages. Our findings suggest that recruited monocyte derived, but not resident macrophages are responsible for the influenza-induced acute lung injury. We also discovered that beta2AR signaling in macrophages may regulate influenza-induced metabolic changes, which are required for pro-inflammatory response against influenza suggested by attenuation of inflammation with inhibitors of glycolysis Hk2 and carbonic anhydrase Ca2.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE