PECAM-1 |
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PECAM-1 (Platelet-Endothelial
Cell Adhesion Molecule-1, CD31) is critical in passage through the junction
in cytokine-activated transmigration. Anti-PECAM-1 antibodies reduce monocyte
transmigration through resting endothelium,
and both monocyte and neutrophil transmigration through cytokine activated
endothelium by 70-90% (Muller,
1995; Muller
et al 1993). Binding of leukocytes to endothelium is not affected.
The effects are seen if endothelial cells or leukocytes or both are treated
with antibodies, and inhibition lasts at least 48 hours (Bogen
et al 1994; Muller,
1995). The efficacy of PECAM-1 antibodies in vivo has been confirmed
in other inflammatory models (Vaporciyan
et al 1993; Muller,
1995). Monoclonal antibodies mapped to domain 1-2 inhibit transmigration,
but other monoclonal antibodies are not inhibitory (Liao
et al 1995). Although v‹3
integrin can be a ligand for PECAM-1 (Piali
et al 1995), and monocytes lacking ‹3-integrin transmigrate poorly,
this appears to be due to modulation of CD11a/CD18 rather than by an interaction
with PECAM-1. Unlike many other endothelial cell adhesion molecules expression
is not significantly upregulated by activation with TNF or IFN-g in usual
doses (Romer
et al 1995). Furthermore, PECAM-1 does not appear to be redistributed
during cytokine or chemotactic transmigration (Allport
et al. 1997).
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