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Persistent pulmonary inflammation and cyclooxygenase ‐1 and ‐2 modifications in alveolar macrophages following in vivo phagocytosis of mycobacteria
Author(s) -
Shibata Yoshimi,
Henriksen Ruth Ann,
Myrvik Quentin N,
Patel Harni,
Pavlovic Mirjana D.,
Shinohara Shizuka,
Pantuso Traci,
Shinohara Tsutomu
Publication year - 2008
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.22.1_supplement.860.5
Subject(s) - phagocytosis , inflammation , in vivo , nasal administration , lung , immune system , western blot , cyclooxygenase , immunology , medicine , chemistry , pathology , enzyme , biology , biochemistry , microbiology and biotechnology , gene
Granuloma formation is a hallmark of mycobacterial infections and represents the histological correlate of both protective immunity and inflammatory tissue destruction. PGE 2 is known to regulate infections, inflammation and tissue repair, although exact mechanisms regulating COX‐2 activity, a rate‐limiting enzyme for PGE 2 biosynthesis, are unclear. In this study, alveolar macrophages (MØ) were isolated from C57Bl/6 mice following intranasal administration of 0.5 mg killed Mycobacteirum bovis BCG. We found that normal alveolar MØ showed minimal (or undetectable) levels of COX‐1 and COX‐2 by western blot. However, one day after administration, almost all MØ had phagocytosed BCG and expressed significant levels of COX‐1 and COX‐2. Analysis by confocal microscopy indicated that for MØ phagocytosing BCG, COX‐1 and COX‐2 were preferentially dissociated from the nuclear envelop (NE), indicating forms catalytically inactive for PGE 2 synthesis. In contrast to mice given ip BCG where peritoneal MØ containing BCG disappeared within 7 days, 28 days after intranasal administration, 68% of alveolar MØ in lung lavage fluid still contained BCG together with NE‐dissociated COX‐1 and COX‐2. Our results indicate that the lack of PGE 2 production may enhance PGE 2 ‐sensitive, MØ c‐mediated immune responses against pulmonary infections and inflammation caused by mycobacteria. [NIH HL71711 and DOD DAMD17‐03‐1‐0004]