Upregulation of SR-PSOX/CXCL16 and recruitment of CD8+ T cells in cardiac valves during inflammatory valvular heart disease.
OBJECTIVE
SR-PSOX/CXCL16 is a transmembrane chemokine and is implicated in activated CD8+ T cell trafficking. In the present study, we examined the expression pattern of SR-PSOX/CXCL16 in the heart and investigated a potential role of SR-PSOX/CXCL16 in inflammatory valvular heart disease.


RESULTS
Initial expression of SR-PSOX/CXCL16 in murine embryos was detected in endothelial cells lining endocardial cushions in the forming heart at E11.5. From mid-gestation to adult, expression of this gene in the heart was exclusively observed in valvular endothelial cells. Examination of SR-PSOX/CXCL16 expression in human cardiac valves demonstrated that SR-PSOX/CXCL16 was strongly expressed in valvular and neocapillary endothelial cells in patients with infective endocarditis. SR-PSOX/CXCL16 expression in neocapillary endothelial cells was also observed in patients with rheumatic and atherosclerotic valvular disease. Moreover, CD8+ T cells were distributed closely to endothelial cells expressing SR-PSOX/CXCL16. In vitro adhesion assays showed that SR-PSOX/CXCL16 induced adhesion of activated CD8+ T cells to vascular cell adhesion molecule-1 (VCAM-1) through very late antigen-4 (VLA-4) activation. Furthermore, SR-PSOX/CXCL16 stimulated interferon-gamma (IFN-gamma) production by CD8+ T cells.


CONCLUSIONS
SR-PSOX/CXCL16 may be involved in CD8+ T cell recruitment through VLA-4 activation and stimulation of IFN-gamma production by CD8+ T cells during inflammatory valvular heart disease.
Yamauchi
Ryoko
R
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Tanaka
Makoto
M
Kume
Noriaki
N
Minami
Manabu
M
Kawamoto
Takahiro
T
Togi
Kiyonori
K
Shimaoka
Takeshi
T
Takahashi
Shu
S
Yamaguchi
Junko
J
Nishina
Takeshi
T
Kitaichi
Masanori
M
Komeda
Masashi
M
Manabe
Toshiaki
T
Yonehara
Shin
S
Kita
Toru
T
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D016466:CHO Cells / Q000737:chemistry / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D006224:Cricetinae; D004622:Embryo, Mammalian / Q000737:chemistry; D004697:Endocarditis, Bacterial / Q000150:complications / Q000473:pathology; D004730:Endothelium, Vascular / Q000737:chemistry / Q000382:microbiology / Q000473:pathology; D005260:Female; D006349:Heart Valve Diseases / Q000209:etiology / Q000473:pathology*; D006351:Heart Valves / Q000737:chemistry / Q000382:microbiology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D039041:Integrin alpha4beta1 / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016612:Paraffin Embedding; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D012213:Rheumatic Fever / Q000150:complications* / Q000473:pathology; D013154:Spleen / Q000737:chemistry; D014162:Transfection / Q000379:methods; D015854:Up-Regulation / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D019743:Chemokines, CXC; C498926:Cxcl16 protein, mouse; D039041:Integrin alpha4beta1; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D019010:Vascular Cell Adhesion Molecule-1; D007371:Interferon-gamma