Lymphocyte function antigen 1 (LFA-1) mediates early tumour necrosis factor alpha-induced leucocyte adhesion in venules.
A co-ordinated expression of specific adhesion molecules regulates leucocyte-endothelium interactions in the microcirculation. In the present study, we used intravital microscopy of the cremaster muscle in CD11a gene-targeted mice to examine the role of lymphocyte function antigen 1 (LFA-1, CD11a/CD18) in tumour necrosis factor alpha (TNF-alpha)-induced leucocyte rolling and firm adhesion in venules. We found that 30 min after TNF-alpha administration leucocyte rolling was unchanged compared with phosphate-buffered saline (PBS)-treated mice and similar in LFA-1-deficient and wild-type animals. In contrast, firm leucocyte adhesion in venules increased by almost 10-fold following 30 min of TNF-alpha challenge in LFA-1-expressing animals, whereas no increase was observed in LFA-1-deficient mice. Four hours after intrascrotal administration of TNF-alpha, venular leucocyte adhesion was found to be markedly increased, but similar in extent to LFA-1-deficient and wild-type mice. Histological examination of haematoxylin-eosin-stained tissue sections revealed that approximately 90% of the leucocytes in the TNF-alpha-stimulated venules in both wild-type and LFA-1-deficient mice were polymorphonuclear. Taken together, our functional in vivo data demonstrate that LFA-1 is an important adhesion molecule in early TNF-alpha-induced venular leucocyte adhesion.
Thorlacius
H
H
Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden.
Vollmar
B
B
Guo
Y
Y
Mak
T W
TW
Pfreundschuh
M M
MM
Menger
M D
MD
Schmits
R
R
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D007962:Leukocytes / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014699:Venules / Q000502:physiology*
D016169:Lymphocyte Function-Associated Antigen-1; D014409:Tumor Necrosis Factor-alpha