Activation and Function of Alternatively and Classically Activated MH-S Alveolar Macrophages

Alveolar macrophages (AMs), the tissue dwelling monocytes of the lungs, are the first to encounter the menagerie of items that pass the mechanical barriers of the nose and throat. AMs must be able to mount an effective immune response against invading pathogens as well as maintain homeostasis in the lungs to avoid excessive inflammatory responses. In vivo data suggests that AMs can take on different phenotypes depending on the conditions of simulation. Limited progress has been made in defining the mechanisms responsible for these phenotypic issues largely due to logistical difficulties in isolating a sufficient number of cells from the lungs that have not been activated by the isolation protocol. To circumvent these logistical issues, an in vitro cell culture model was developed to study AM biology with specific emphasis on the generation of alternatively activated alveolar macrophages (AAAMs). Utilizing the BALB/c AM cell line MH-S it was determined that LPS could be used to generate classically activated AMs (CAAMs) and that IL-4 was effective in producing AAAMs. We examined the full transcriptome of AAAMs and CAAMs using microarray technology in an attempt to confirm previously described AAAM expression patterns and to identify new molecules associated with AM phenotypic change. AAAMs up-regulated an entirely distinct group of transcripts including genes encoding Arg1, Ym1 and a number of repair and remodeling genes whereas CAAMs up-regulated proinflammatory cytokines such as IL-1, IL-6 and IL-12. Additional novel markers are identified in this study to better characterize CAAMs and AAAMs in the lung.

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