title: Pig bone marrow-derived macrophages resemble human macrophages in their response to bacterial lipopolysaccharide.
abstract: Mouse bone marrow-derived macrophages (BMDM) grown in M-CSF (CSF-1) have been used widely in studies of macrophage biology and the response to TLR agonists. We investigated whether similar cells could be derived from the domestic pig using human rCSF-1 and whether porcine macrophages might represent a better model of human macrophage biology. Cultivation of pig bone marrow cells for 5-7 d in presence of human rCSF-1 generated a pure population of BMDM that expressed the usual macrophage markers (CD14, CD16, and CD172a), were potent phagocytic cells, and produced TNF in response to LPS. Pig BMDM could be generated from bone marrow cells that had been stored frozen and thawed so that multiple experiments can be performed on samples from a single animal. Gene expression in pig BMDM from outbred animals responding to LPS was profiled using Affymetrix microarrays. The temporal cascade of inducible and repressible genes more closely resembled the known responses of human than mouse macrophages, sharing with humans the regulation of genes involved in tryptophan metabolism (IDO, KYN), lymphoattractant chemokines (CCL20, CXCL9, CXCL11, CXCL13), and the vitamin D3-converting enzyme, Cyp27B1. Conversely, in common with published studies of human macrophages, pig BMDM did not strongly induce genes involved in arginine metabolism, nor did they produce NO. These results establish pig BMDM as an alternative tractable model for the study of macrophage transcriptional control.
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK.
authors.forename: Ronan
authors.initials: R
authors.lastname: Kapetanovic
authors.forename: Lynsey
authors.initials: L
authors.lastname: Fairbairn
authors.forename: Dario
authors.initials: D
authors.lastname: Beraldi
authors.forename: David P
authors.initials: DP
authors.lastname: Sester
authors.forename: Alan L
authors.initials: AL
authors.lastname: Archibald
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Tuggle
authors.forename: David A
authors.initials: DA
authors.lastname: Hume
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology; D053263:Gene Regulatory Networks; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000032:analysis; D020411:Oligonucleotide Array Sequence Analysis; D010587:Phagocytosis / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D019779:Salmonella enterica; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D034421:Sus scrofa / Q000033:anatomy & histology / Q000276:immunology*
chemical_list: D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D009569:Nitric Oxide; D016173:Macrophage Colony-Stimulating Factor