An anti-platelet-endothelial cell adhesion molecule-1 antibody inhibits leukocyte extravasation from mesenteric microvessels in vivo by blocking the passage through the basement membrane.

Abstract

SummaryPlatelet-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 anti-PECAM-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.

A Novel Anionic Modification of N-Glycans on Mammalian Endothelial Cells Is Recognized by Activated Neutrophils and Modulates Acute Inflammatory Responses

“…Several in vitro and in vivo studies have shown that PECAM-1 (CD31) is critically involved in transendothelial migration (15). Interestingly, Abs against PECAM-1 inhibit leukocyte extravasation from mesenteric vessels (16,17), similar to the effects of mAb GB3.1 seen in our studies. However, the expression patterns of CD31 on the surface of most leukocytes, platelets, and intercellular junctions of endothelial cells (15) is different from that of the GB3.1 Ags.…”

Effects of the prebiotics inulin and lactulose on intestinal immunology and hematology of preruminant calves

“…PECAM1 is a cell-surface molecule of leukocytes and endothelial cells and is crucial for the transmigration of leukocytes through the capillary wall into inflamed tissue (Wakelin et al, 1996), which rather stands for pro-inflammatory action. Nevertheless, it has been found to be downregulated on endothelial cells in typical pro-inflammatory situations such as stimulation with TNF or IFN-g without effect on leukocyte transmigration (Shaw et al, 2001).…”

Change in platelet endothelial cell adhesion molecule-1 immunoreactivity in the dentate gyrus in gerbils fed a folate-deficient diet

“…It has also been reported that neutrophil transmigration and macromolecular leakage are increased in the ischemia/ reperfusion group, whereas that the increase is attenuated in the animals treated with anti-PECAM-1 antibodies [32][33][34]. In brief, the elevation of PECAM-1 immunoreactivity and protein level in the gerbil ischemic dentate gyrus of the FAD-treated gerbils may be associated with an acceleration of ischemic damage.…”

“…It has been reported that the expression of PECAM-1 or other cell adhesion molecules were increased in the spinal cord ischemia [4], focal cerebral ischemia [9,29], and other peripheral ischemia models [31,33,34]. The elevation of PECAM-1 immunoreactivity and its protein level in vessels increases the transmigration of lymphocytes and neutrophils [6,27].…”

“…The microcirculatory disturbance may be induced by forming capillary block, BBB damage, vasoconstriction, biochemical mediators such as reactive oxygen species (ROS), leukotrienes, cytokines, plateletactivating factor, and proteolytic enzymes stemming from interaction between leukocytes and perturbed endothelium in the ischemic region [9,33].…”