title: Susceptibility to experimental Lyme arthritis correlates with KC and monocyte chemoattractant protein-1 production in joints and requires neutrophil recruitment via CXCR2.
abstract: The development of experimental Lyme arthritis has been correlated with the expression of a number of chemokines and cytokines, however, none of these have been measured directly from the arthritic joint. We examined the temporal expression of IL-1beta, IL-4, IL-6, IL-10, IL-12p70, GM-CSF, IFN-gamma, TNF-alpha, macrophage inflammatory protein-2, KC, macrophage inflammatory protein-1alpha, and monocyte chemoattractant protein-1 directly from the tibiotarsal joint in arthritis-resistant C57BL/6 (B6) and -susceptible C3H/He (C3H) mice. Only the chemokines KC and monocyte chemoattractant protein-1 were differentially expressed in joints of B6 and C3H mice and correlated with the development of Lyme arthritis. Infection of CXCR2(-/-) mice on either genetic background resulted in a significant decrease in the development of pathology, although infection of CCR2(-/-) mice had little or no effect. Neutrophils in CXCR2(-/-) mice were marginalized within blood vessels and could not enter the joint tissue. These results suggest that chemokine-mediated recruitment of neutrophils into the infected joint is a key requirement for the development of experimental Lyme arthritis.
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65211, USA. BrownChar@missouri.edu
authors.forename: Charles R
authors.initials: CR
authors.lastname: Brown
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Blaho
authors.forename: Christie M
authors.initials: CM
authors.lastname: Loiacono
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D025065:Borrelia burgdorferi / Q000276:immunology*; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000378:metabolism; D054360:Chemokine CXCL1; D018925:Chemokines / Q000096:biosynthesis; D019743:Chemokines, CXC; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006614:Hindlimb; D008193:Lyme Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000235:genetics / Q000276:immunology*; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics; D023063:Receptors, Interleukin-8B / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012720:Severity of Illness Index; D013583:Synovial Membrane / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; D016207:Cytokines; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D023063:Receptors, Interleukin-8B; C074302:keratinocyte-derived chemokines