title: CINC-1 is an acute-phase protein induced by focal brain injury causing leukocyte mobilization and liver injury.
abstract: Following injury or infection, the liver releases acute-phase proteins (APP). After a severe focal injury, this systemic response can be excessive and may lead to multiorgan dysfunction (MODS). CINC-1 is a neutrophil chemoattractant, and we have now established that it also functions as an early APP after injury to the brain or to peripheral tissues. After induction of a focal inflammatory lesion in the brain, there is rapid hepatic and serum CINC-1 induction, which is associated with increases in neutrophil numbers within the liver and within the circulation. CINC-1-mediated recruitment of neutrophils to organs distant from the primary injury site may contribute to MODS. Indeed, we found that enzyme markers of liver tissue injury are increased in the serum following generation of a focal inflammatory lesion in the brain. Neutralization of CINC-1 in the periphery reversed brain-injury-induced neutrophil mobilization and inhibited recruitment of neutrophils to the brain and to the liver. Thus, a significant component of the hepatic acute-phase response is the release of chemokines by the liver, which act to amplify the inflammatory response and modulate the subsequent leukocytosis and secondary tissue damage. Hepatic CINC-1 synthesis following injury presents a novel focus for treatment of inflammation.
authors.affiliation: Molecular Neuropathology Laboratory, School of Biological Sciences, University of Southampton, Biomedical Sciences Building, Southampton S016 7PX, UK. s.j.campbell@soton.ac.uk
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Campbell
authors.forename: Paula M
authors.initials: PM
authors.lastname: Hughes
authors.forename: John P
authors.initials: JP
authors.lastname: Iredale
authors.forename: David C
authors.initials: DC
authors.lastname: Wilcockson
authors.forename: Sara
authors.initials: S
authors.lastname: Waters
authors.forename: Fabian
authors.initials: F
authors.lastname: Docagne
authors.forename: V Hugh
authors.initials: VH
authors.lastname: Perry
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Anthony
mesh_terms: D000209:Acute-Phase Proteins / Q000096:biosynthesis / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000276:immunology; D001927:Brain Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D054360:Chemokine CXCL1; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D005786:Gene Expression Regulation; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007375:Interleukin-1 / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000276:immunology* / Q000473:pathology; D008954:Models, Biological; D009504:Neutrophils / Q000276:immunology*; D051381:Rats; D000637:Transaminases / Q000097:blood
chemical_list: D000209:Acute-Phase Proteins; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C513297:Cxcl1 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D000637:Transaminases