Two-step model of leukocyte-endothelial cell interaction in inflammation: distinct roles for LECAM-1 and the leukocyte beta 2 integrins in vivo.
The lectin homing receptor LECAM-1 (LAM-1, Leu8) and the beta 2 integrins, particularly Mac-1 (CD11b/CD18), participate in leukocyte-endothelial cell interactions in inflammation. LECAM-1 is rapidly shed while Mac-1 expression is dramatically increased upon neutrophil activation, suggesting functionally distinct roles for these molecules. Using intravital video microscopy, we have compared the effect of antibodies against LECAM-1 and CD18 on leukocyte interactions with rabbit mesenteric venules. Anti-LECAM-1 monoclonal antibody and its Fab fragments inhibited initial reversible leukocyte rolling along the vascular wall. Anti-CD18 monoclonal antibody had no effect on rolling but prevented subsequent firm attachment of leukocytes to venular endothelium. These results support a two-step model of leukocyte-endothelial cell interactions: reversible rolling mediated in part by LECAM-1 facilitates leukocyte recruitment by the local microenvironment and precedes activation-dependent firm attachment involving beta 2 integrins.
von Andrian
U H
UH
La Jolla Institute for Experimental Medicine, CA 92037.
Chambers
J D
JD
McEvoy
L M
LM
Bargatze
R F
RF
Arfors
K E
KE
Butcher
E C
EC
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000502:physiology*; D018821:CD18 Antigens; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D004730:Endothelium, Vascular / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments; D066298:In Vitro Techniques; D007249:Inflammation / Q000276:immunology*; D019041:L-Selectin; D007962:Leukocytes / Q000276:immunology*; D008297:Male; D008954:Models, Biological; D011817:Rabbits; D016028:Receptors, Leukocyte-Adhesion / Q000502:physiology*; D013152:Splanchnic Circulation; D014699:Venules / Q000503:physiopathology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D007140:Immunoglobulin Fab Fragments; D016028:Receptors, Leukocyte-Adhesion; D019041:L-Selectin