Transendothelial migration and trafficking of leukocytes in LFA-1-deficient mice.
The leukocyte integrin LFA-1 plays an important role in leukocyte trafficking and the immune response. Using LFA-1-deficient mice, we demonstrate that LFA-1 regulates the trafficking of lymphocytes to peripheral 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, plays a vital role in T lymphocyte and neutrophil transendothelial migration. Neutrophils and activated T lymphocytes from LFA-1-deficient mice were unable to cross endothelial cell monolayers in response to a chemokine gradient, whereas wild-type (WT) T lymphocytes and neutrophils were capable of migration. By contrast, LFA-1-deficient T lymphocytes displayed normal chemotaxis to the same chemokine. Our studies with LFA-1-deficient monocytes indicate that LFA-1 acts in concert with complement receptor 3 to mediate transendothelial migration of these cells, as anti-CD18 monoclonal antibodies (mAb) blocked both WT and LFA-1-deficient monocyte transendothelial migration, whereas anti-CD11 b mAb preferentially blocked transendothelial migration of LFA-1-deficient monocytes. Finally, whereas anti-CD31 mAb blocked WT monocyte and neutrophil transendothelial cell migration they did not block LFA-1-deficient monocyte and neutrophil transendothelial migration.
Andrew
D P
DP
Amgen Inc., Boulder, USA. dpandrew@hotmail.com
Spellberg
J P
JP
Takimoto
H
H
Schmits
R
R
Mak
T W
TW
Zukowski
M M
MM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D006968:Hypersensitivity, Delayed; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D007962:Leukocytes / Q000502:physiology; D008198:Lymph Nodes; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D016177:Macrophage-1 Antigen / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen