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A novel role of macrophages in turning‐off endotoxin‐induced neutrophiliclung inflammation and thereby preventing acute lung injury associated withGram negative bacteria
Author(s) -
Chava Koteswara Rao,
Mohammad Tauseef,
Mehta Dolly
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1017.3
Subject(s) - inflammation , lung , infiltration (hvac) , sepsis , diphtheria toxin , medicine , edema , immunology , macrophage , pulmonary edema , pharmacology , chemistry , toxin , in vitro , biology , microbiology and biotechnology , biochemistry , physics , thermodynamics
Acute lung injury (ALI) associated with Gram‐negative bacterial sepsis is a life threatening neutrophilc inflammatory lung (NLI) disease. In this study, we used transgenic CD11b‐diphtheria toxin receptor (DTR) mice whereby administration of Diphtheria toxin (DT) selectively depletes macrophages/monocytes by inducing apoptosis to investigate the role of macrophage in NLI. We confirmed that DT injection significantly depleted F4/80+ cells in the BAL fluid and markedly reduced monocyte in the blood without altering other cell type. Control mice and DT mice were then exposed to nebulized LPS for an hour, after which lung inflammation was determined at 4, 24 and 48 hrs post LPS challenge. We show that WT lungs develop edema and NLI within 4 hrs after LPS challenge and which is resolved within next 24 hrs, reached near the basal levels in 48 hrs. Surprisingly, DT mice displayed delayed neutrophilic inflammation i.e. there was no lung edema and neutrophil infiltration at 4 hrs after LPS challenge and they were evident at 24 hrs, and NLI did not resolve even at 48 hrs. Further CD11 mice were subjected to LPS inhalation and then DT was given. We show that depletion of macrophages post LPS‐induced injury produce persistent NLI and lung edema. These data suggest that macrophages play a vital role in the autoregulaory loop of resolution of inflammatory process and thereby play a fundamental role in preventing the lung injury.