Quantitative In-Depth Transcriptome Analysis Implicates Peritoneal Macrophages as Important Players in the Complement and Coagulation Systems

To obtain a more detailed picture of macrophage (M phi) biology, in the current study, we analyzed the transcriptome of mouse peritoneal M phi s by RNA-seq and PCR-based transcriptomics. The results show that peritoneal M phi s, based on mRNA content, under non-inflammatory conditions produce large amounts of a number of antimicrobial proteins such as lysozyme and several complement components. They were also found to be potent producers of several chemokines, including platelet factor 4 (PF4), Ccl6, Ccl9, Cxcl13, and Ccl24, and to express high levels of both TGF-beta 1 and TGF-beta 2. The liver is considered to be the main producer of most complement and coagulation components. However, we can now show that M phi s are also important sources of such compounds including C1qA, C1qB, C1qC, properdin, C4a, factor H, ficolin, and coagulation factor FV. In addition, FX, FVII, and complement factor B were expressed by the M phi s, altogether indicating that M phi s are important local players in both the complement and coagulation systems. For comparison, we analyzed human peripheral blood monocytes. We show that the human monocytes shared many characteristics with the mouse peritoneal M phi s but that there were also many major differences. Similar to the mouse peritoneal M phi s, the most highly expressed transcript in the monocytes was lysozyme, and high levels of both properdin and ficolin were observed. However, with regard to connective tissue components, such as fibronectin, lubricin, syndecan 3, and extracellular matrix protein 1, which were highly expressed by the peritoneal M phi s, the monocytes almost totally lacked transcripts. In contrast, monocytes expressed high levels of MHC Class II, whereas the peritoneal M phi s showed very low levels of these antigen-presenting molecules. Altogether, the present study provides a novel view of the phenotype of the major M phi subpopulation in the mouse peritoneum and the large peritoneal M phi s and places the transcriptome profile of the peritoneal M phi s in a broader context, including a comparison of the peritoneal M phi transcriptome with that of human peripheral blood monocytes and the liver.