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

Thorlacius, H.
Vollmar, B.
Guo, Y.
Mak, T. W.
Pfreundschuh, M. M.
Menger, M. D.
Schmits, R.

¹Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden, ²Institute for Clinical and Experimental Surgery, University of Saarland, Homburg, Germany, ³Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden, ⁴Department of Immunology, University of Toronto, Toronto, Ontario, Canada, and ⁵Department of Internal Medicine, University of Saarland, Homburg, Germany

Received 28 December 1999; accepted for publication 24 March 2000

Correspondence: Rudolf Schmits, Department of Internal Medicine, University of Saarland, 66421 Homburg/Saar, Germany. E-mail: [email protected]

British Journal of Haematology 110(2):p 424-429, August 2000.

Summary.

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 α (TNF-α)-induced leucocyte rolling and firm adhesion in venules. We found that 30 min after TNF-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 TNF-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 TNF-α-induced venular leucocyte adhesion.