학술논문
Multi-Omic blood analysis reveals differences in innate inflammatory sensitivity between species.
Document Type
Author
Gregory DJ; Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; Han F; Harvard Medical School, Boston, MA, USA.; Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Li P; Harvard Medical School, Boston, MA, USA.; Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Gritsenko M; Biological Sciences Division, Pacific Northwest National Laboratory, Richland WA, USA.; Kyle J; Biological Sciences Division, Pacific Northwest National Laboratory, Richland WA, USA.; Riley FE; Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA.; Chavez D; Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio TX, USA.; Yotova V; Centre Hospitalier Universitaire Sainte-Justine, Montréal, Québec, Canada.; Sindeaux RHM; Centre Hospitalier Universitaire Sainte-Justine, Montréal, Québec, Canada.; Hawash MBF; Centre Hospitalier Universitaire Sainte-Justine, Montréal, Québec, Canada.; Department of Biochemistry, University of Montréal, Montréal, Québec, Canada.; Xu F; Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA.; Hung LY; Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Hayden DL; Harvard Medical School, Boston, MA, USA.; Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Tompkins RG; Harvard Medical School, Boston, MA, USA.; Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Lanford RE; Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio TX, USA.; Kobzik L; Program in Molecular and Integrative Physiological Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA.; Hellman J; Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA.; Jacobs JM; Biological Sciences Division, Pacific Northwest National Laboratory, Richland WA, USA.; Barreiro LB; Centre Hospitalier Universitaire Sainte-Justine, Montréal, Québec, Canada.; Department of Biochemistry, University of Montréal, Montréal, Québec, Canada.; Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA.; Department of Human Genetics, University of Chicago, Chicago, IL, USA.; Committee on Genetics, Genomics, and Systems Biology, University of Chicago, Chicago, IL, USA.; Committee on Immunology, University of Chicago, Chicago, IL, USA.; Xiao W; Harvard Medical School, Boston, MA, USA.; Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Warren HS; Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; Department of Medicine, Massachusetts General Hospital, Boston, MA.
Source
Country of Publication: United States NLM ID: 101767986 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: medRxiv Subsets: PubMed not MEDLINE
Subject
Language
English
Abstract
Vertebrates differ greatly in responses to pro-inflammatory agonists such as bacterial lipopolysaccharide (LPS), complicating use of animal models to study human sepsis or inflammatory disorders. We compared transcriptomes of resting and LPS-exposed blood from six LPS-sensitive species (rabbit, pig, sheep, cow, chimpanzee, human) and four LPS-resilient species (mice, rats, baboon, rhesus), as well as plasma proteomes and lipidomes. Unexpectedly, at baseline, sensitive species already had enhanced expression of LPS-responsive genes relative to resilient species. After LPS stimulation, maximally different genes in resilient species included genes that detoxify LPS, diminish bacterial growth, discriminate sepsis from SIRS, and play roles in autophagy and apoptosis. The findings reveal the molecular landscape of species differences in inflammation, and may inform better selection of species for pre-clinical models.
Competing Interests: Competing interests: Authors declare that they have no competing interests.
Competing Interests: Competing interests: Authors declare that they have no competing interests.