Alveolar Macrophage Programming Following Endotoxin Exposure

National Jewish Health25 enrolled

Overview

The histologic hallmarks of lung inflammation include accumulation of inflammatory cells in the airspaces and interstitium, injury to alveolar epithelial and endothelial cells, loss of epithelial-capillary integrity and accumulation of edema fluid in the interstitium and airspaces. Accordingly, for alveolar repair to occur inflammation must be halted, debris and inflammatory cells removed, injured tissue cells replaced, and capillary barrier function re-established. Macrophages are key players in all of these. Here the investigators hypothesize that resident alveolar macrophages and recruited macrophages serve completely different functions, acting independently (i.e. division of labor) yet cooperatively (synergism).

Study Type

INTERVENTIONAL

Allocation

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

ARDS, Human

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. Written, informed consent 2. Age 18-50 Exclusion Criteria: 1. Current or recent illness (past 2 weeks) 2. Presence or prior history of cardiac, pulmonary or systemic disease 3. Bleeding disorder, use of systemic anticoagulants or antiplatelet therapy 4. American Society of Anesthesiology (ASA) class 2 or greater 5. Immunocompromised state (HIV, immunoglobulin deficiency, systemic immunosuppressants) 6. Use of any inhaled substance, including tobacco, marijuana, e-cigarrettes, cocaine, methamphetamines, or toxic vapors in the past 3 months or greater than 10 pack-year smoking history 7. Alcohol use disorder or greater than 7 drinks/week for women or greater than 14 drinks/week for men in the past 3 months 8. Allergy or prior adverse reaction to lidocaine, midazolam or fentanyl 9. Abnormal spirometry or electrocardiogram at time of screening 10. Pregnant (based on urine pregnancy test) or breast feeding

Outcomes

Primary Outcomes

Resident alveolar macrophages and recruited macrophages will be distinguished from one another using multi-parameter flow cytometry, and the relative proportions enumerated

Resident and recruited macrophages will be purified using fluorescence activated cell sorting (FACS) and subjected to RNA sequencing.

Time frame: 7 days