Platelet-endothelial cell adhesion molecule-1 (PECAM-1, CD31) plays an active role in the
process of leukocyte migration through cultured endothelial cells in vitro and anti-PECAM-1
antibodies (Abs) inhibit accumulation ofleukocytes into sites of inflammation in vivo. Despite
the latter, it is still not clear at which stage of leukocyte emigration in vivo PECAM-1 is involved.
To address this point directly, we studied the effect of an anti-PECAM-1 Ab, recognizing
rat PECAM-1, on leukocyte responses within rat mesenteric microvessels using intravital
microscopy. In mesenteric preparations activated by interleukin (IL)-113, the anti-PECAM-1
Ab had no significant effect on the rolling or adhesion ofleukocytes, but inhibited their migration
into the surrounding extravascular tissue in a dose-dependent manner. Although in some
vessel segments these leukocytes had come to a halt within the vascular lumen, often the leukocytes
appeared to be trapped within the vessel wall. Analysis of these sections by electron microscopy
revealed that the leukocytes had passed through endothelial cell junctions but not the
basement membrane. In contrast to the effect of the Ab in mesenteric preparations treated with
IL-113, leukocyte extravasation induced by topical or intraperitoneal administration of the
chemotactic peptide formyl-methionyl-leucyl-phenylalanine was not inhibited by the antiPECAM-1
Ab. These results directly demonstrate a role for PECAM-1 in leukocyte extravasation
in vivo and indicate that this involvement is selective for leukocyte extravasation elicited
by certain inflammatory mediators. Further, our findings provide the first in vivo indication
that PECAM-1 may have an important role in triggering the passage of leukocytes through the
perivascular basement membrane.