Dp. Andrew et al., TRANSENDOTHELIAL MIGRATION AND TRAFFICKING OF LEUKOCYTES IN LFA-1-DEFICIENT MICE, European Journal of Immunology, 28(6), 1998, pp. 1959-1969
The leukocyte integrin LFA-1 plays an important role in leukocyte traf
ficking and the immune response. Using LFA-1-deficient mice, we demons
trate that LFA-1 regulates the trafficking of lymphocytes to periphera
l lymph nodes, and, to a lesser degree, to mesenteric lymph nodes and
acute inflammatory sites. LFA-1, either because of its role in initial
adhesion and/or the passage of leukocytes across endothelial cells, p
lays a vital role in T lymphocyte and neutrophil transendothelial migr
ation. Neutrophils and activated T lymphocytes from LFA-1-deficient mi
ce were unable to cross endothelial cell monolayers in response to a c
hemokine gradient, whereas wild-type (WT) T lymphocytes and neutrophil
s were capable of migration. By contrast, LFA-1-deficient T lymphocyte
s displayed normal chemotaxis to the same chemokine. Our studies with
LFA-1-deficient monocytes indicate that LFA-1 acts in concert with com
plement receptor 3 to mediate transendothelial migration of these cell
s, as anti-CD18 monoclonal antibodies (mAb) blocked both WT and LFA-1-
deficient monocyte transendothelial migration, whereas anti-CD11b mAb
preferentially blocked transendothelial migration of LFA-1-deficient m
onocytes. Finally, whereas anti-CD31 mAb blocked WT monocyte and neutr
ophil transendothelial cell migration they did not block LFA-1-deficie
nt monocyte and neutrophil transendothelial migration.