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Epigenetic Regulation of Macrophage Linage During Acute Lung Injury and Resolution
Author(s) -
Rochford Ian,
Joshi Jagdish C,
Mehta Dolly
Publication year - 2017
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.31.1_supplement.871.5
Subject(s) - cd11c , macrophage , lung , population , haematopoiesis , integrin alpha m , bronchoalveolar lavage , immunology , medicine , inflammation , bone marrow , biology , pathology , microbiology and biotechnology , immune system , phenotype , in vitro , stem cell , genetics , gene , environmental health
Macrophages coordinate both the initiation and resolution of acute lung injury (ALI), a chronic lung disease which causes significant mortality and morbidity. Macrophages are divided into multiple functionally plastic and phenotypically distinct subpopulations based on their differences in anatomical location and cytokine signaling. Here, we used a mouse model which expresses GFP under the control of the myeloid‐specific Lys‐M promoter and exposed them to pneumonia‐induced ALI to identify shifts in macrophages lineage during inflammatory and resolution phases of lung injury. Flow cytometric analysis showed a dynamic shift in macrophages subpopulations on the onset versus resolution of injury. We found that in naïve lungs, CD11c+/Cd11b+ macrophages, which represent both recruited and lung resident macrophage populations, represent 24.45% of total lung hematopoietic cells. At 4 hours post LPS inhalation, which marks the peak of injury phase, this population decreased to 6.7%. C11b+/CD11c+ then rebound back and their number increased to 59.34% and 49.74% respectfully, during resolution of injury at 24 and 48 hours. On the other hand, CD11c+/CD11b‐macrophages, which constitute alveolar macrophages population, continue to drop from a value of 34.6% at basal state to 29.5% during injury at 4 hours and to 5.9% at 24 hours post LPS. Interestingly, a CD11c+/CD11b (Low) population emerged at 48 hours amounting 17.9% of total macrophages. QPCR analysis of lungs indicated an increase in the expression of HDAC1, an epigenetic modifying enzyme, also at 48 hours. LyzM‐GFP bone marrow derived macrophages also showed distinct morphological phenotypic changes after stimulation with LPS from 0, 4, 18 and 24 hours, indicating differential lineage. We propose that characterization of the genetic and phenotypic signatures of CD11b/Cd11c macrophages of different lineages which disappear and emerge during the onset of injury and resolution phase of ALI may provide insight to their therapeutic potential as a cell‐based therapy for resolving ALI. Support or Funding Information Supported by PPG2 2POHL077806‐11 and T32‐HL007829