Two-step model of leukocyte-endothelial cell interaction in inflammation: distinct roles for LECAM-1 and the leukocyte beta 2 integrins in vivo.

TLDR

LECAM‑1 and beta‑2 integrins (particularly Mac‑1) mediate leukocyte‑endothelial interactions, with LECAM‑1 rapidly shed and Mac‑1 upregulated upon neutrophil activation, indicating distinct functional roles. Intravital video microscopy of rabbit mesenteric venules was used to compare the effects of anti‑LECAM‑1 and anti‑CD18 antibodies on leukocyte adhesion. Anti‑LECAM‑1 antibodies blocked initial reversible rolling, whereas anti‑CD18 antibodies inhibited only firm attachment, supporting a two‑step model in which LECAM‑1 mediates rolling and beta‑2 integrins mediate firm adhesion.

Abstract

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.