The role of T-lymphocytes in hypercholesterolemia-induced leukocyte-endothelial interactions.
OBJECTIVE
Hypercholesterolemia promotes the adhesion of leukocytes to vascular endothelium in large and microscopic blood vessels. Lymphocytes that can modulate endothelial cell adhesion molecule expression have been implicated in the altered structure and function of large arterial vessels associated with chronic hypercholesterolemia. This study assesses the contribution of CD4(+) and CD8(+) T-cells to acute inflammatory responses observed in the microcirculation of hypercholesterolemic mice.


METHODS
Intravital microscopy was used to quantify baseline leukocyte-endothelial cell interactions in cremasteric postcapillary venules of wild-type (WT) and severe combined immunodeficient (SCID) mice placed on a normal (ND) or high-cholesterol (HC) diet for 2 weeks. A group of SCID-HC mice received splenocytes from WT-HC mice (WT-->SCID). Separate WT-HC groups were depleted of neutrophils or CD4(+) and/or CD8(+) T-cells.


RESULTS
WT-HC mice, compared with WT-ND, exhibited exaggerated leukocyte adherence and emigration. These leukocytes were predominantly granulocytes. These responses were absent in neutropenic WT-HC mice. SCID-HC mice also showed significantly less leukocyte adherence and emigration than WT-HC mice. Elevated leukocyte adherence and emigration were restored in WT-->SCID mice, despite a continued absence of circulating blood lymphocytes. Selective depletion of either CD4(+) or CD8(+) cell populations attenuated HC-induced leukocyte adhesion but not emigration. However, simultaneous depletion of both CD4(+) and CD8(+) cells attenuated both leukocyte adhesion and emigration to ND levels.


CONCLUSIONS
These findings indicate that both CD4(+) and CD8(+) T-cells contribute to granulocyte adhesion and emigration elicited in postcapillary venules by hypercholesterolemia.
Stokes
Karen Y
KY
Department of Molecular and Cellular Physiology, LSU Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932, USA.
Clanton
E Chris
EC
Bowles
Kimberly S
KS
Fuseler
John W
JW
Chervenak
Deborah
D
Chervenak
Robert
R
Jennings
Stephen R
SR
Granger
D Neil
DN
D000818:Animals; D002448:Cell Adhesion; D002450:Cell Communication / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D004730:Endothelium, Vascular / Q000166:cytology*; D006098:Granulocytes / Q000166:cytology*; D006937:Hypercholesterolemia / Q000473:pathology*; D036904:Leukocyte Rolling; D051379:Mice; D008815:Mice, Inbred Strains; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000502:physiology*; D014699:Venules / Q000166:cytology