Lymphocyte function antigen 1 (LFA-1) mediates early tumour necrosis factor α-induced leucocyte adhesion in venules

Abstract

A coordinated 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 α (TNT-α-induced leucocyte rolling and firm adhesion in venules. We found that 30 min after TNT-α 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-α challenge in LFA-1-expressing animals, whereas no increase was observed in LFA-1-deficient mice. Four hours after intrascrotal administration of TNT-α, 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-α-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 TNT-α-induced venular leucocyte adhesion.