title: Linked chromosome 16q13 chemokines, macrophage-derived chemokine, fractalkine, and thymus- and activation-regulated chemokine, are expressed in human atherosclerotic lesions.
abstract: Chemokines are important mediators of macrophage and T-cell recruitment in a number of inflammatory pathologies, and chemokines expressed in atherosclerotic lesions may play an important role in mononuclear cell recruitment and macrophage differentiation. We have analyzed the expression of the linked chromosome 16q13 genes that encode macrophage-derived chemokine (MDC/CCL22), thymus- and activation-regulated chemokine (TARC/CCL17), and the CX(3)C chemokine fractalkine (CX(3)CL1) in primary macrophages and human atherosclerotic lesions by reverse transcription-polymerase chain reaction and immunohistochemistry. We show that macrophage expression of the chemokines MDC, fractalkine, and TARC is upregulated by treatment with the Th2-type cytokines interleukin-4 and interleukin-13. High levels of MDC, TARC, and fractalkine mRNA expression are seen in some, but not all, human arteries with advanced atherosclerotic lesions. Immunohistochemistry shows that MDC, fractalkine, and TARC are expressed by a subset of macrophages within regions of plaques that contain plaque microvessels. We conclude that MDC, fractalkine, and TARC, which are chromosome 16q13 chemokines, could play a role in mononuclear cell recruitment into atherosclerotic lesions and influence the subsequent inflammatory response. Macrophage-expressed chemokines upregulated by interleukin-4 may be useful surrogate markers for the presence of Th2-type immune responses in human atherosclerotic lesions.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford, UK. david.greaves@path.ox.ac.uk
authors.forename: D R
authors.initials: DR
authors.lastname: Greaves
authors.forename: T
authors.initials: T
authors.lastname: Häkkinen
authors.forename: A D
authors.initials: AD
authors.lastname: Lucas
authors.forename: K
authors.initials: K
authors.lastname: Liddiard
authors.forename: E
authors.initials: E
authors.lastname: Jones
authors.forename: C M
authors.initials: CM
authors.lastname: Quinn
authors.forename: J
authors.initials: J
authors.lastname: Senaratne
authors.forename: F R
authors.initials: FR
authors.lastname: Green
authors.forename: K
authors.initials: K
authors.lastname: Tyson
authors.forename: J
authors.initials: J
authors.lastname: Boyle
authors.forename: C
authors.initials: C
authors.lastname: Shanahan
authors.forename: P L
authors.initials: PL
authors.lastname: Weissberg
authors.forename: S
authors.initials: S
authors.lastname: Gordon
authors.forename: S
authors.initials: S
authors.lastname: Ylä-Hertualla
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001158:Arteries / Q000378:metabolism; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D018929:Cell Culture Techniques; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D054428:Chemokine CX3CL1; D019742:Chemokines, CC / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D020523:Chemokines, CX3C / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D002634:Chemotaxis, Leukocyte; D002885:Chromosomes, Human, Pair 16; D003713:Dendritic Cells / Q000378:metabolism; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D007378:Interleukins / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D018418:Th2 Cells / Q000276:immunology; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C106230:CCL17 protein, human; C515482:CCL22 protein, human; C515538:CX3CL1 protein, human; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D054428:Chemokine CX3CL1; D019742:Chemokines, CC; D020523:Chemokines, CX3C; D007378:Interleukins; D008565:Membrane Proteins; D012333:RNA, Messenger