Expression of endothelial cell adhesion molecules in joints and heart during Borrelia burgdorferi infection of mice.
The expression of adhesion molecules on endothelia was examined during chronic arthritis and carditis in SCID and immunocompetent susceptible AKR/N mice infected with Borrelia burgdorferi (B. burgdorferi). All stages of disease were associated with the upregulation or new expression of ICAM-1 and P-selectin and of VCAM-1 and E-selectin, respectively, on blood vessels of affected joint tissues of SCID and AKR/N mice as well as on heart tissue of SCID mice but not in other tissues. Moreover, ICAM-1 was also found on infiltrating mononuclear cells. The overall staining intensity for each of the four adhesion molecules on individual tissue sections of joint and heart increased with time of infection and was associated with the presence of spirochetes in the tissue. In addition it is shown that in both mouse strains inflammation of joints but not heart is accompanied by vascular proliferation. Synovial but not heart tissues of infected SCID mice were found to express both peripheral- (PNAd) and mucosal (MAdCAM-1) lymph node high endothelia venule associated vascular addressins as detected by mAb Meca-79 and Meca-367, respectively, but only at later stages of the disease and only on newly generated small venules. However, neither of the two addressins were evident in synovial lesions of AKR/N mice. Together the data suggest that the concomittant induction of ICAM-1, VCAM-1, E-selectin and P-selectin in lesions of infected mice provide a means for enhanced cellular infiltration into affected organs and that the regulation of these structures is conserved in the absence of a functional immune system. Furthermore, the differential induction of vascular proliferation in joint and heart tissues as well as the restricted expression patterns of vascular addressins indicate that the pathogenetic processes induced by B. burgdorferi are distinct for joint and heart.
Schaible
U E
UE
Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
Vestweber
D
D
Butcher
E G
EG
Stehle
T
T
Simon
M M
MM
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001170:Arthritis, Infectious / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D019040:E-Selectin; D004697:Endocarditis, Bacterial / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004727:Endothelium / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007596:Joints / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008193:Lyme Disease / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins; D051379:Mice; D008806:Mice, Inbred AKR; D016513:Mice, SCID; D009206:Myocardium / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1
D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D019040:E-Selectin; C069886:L-selectin counter-receptors; D008565:Membrane Proteins; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1