EFFECT OF HISTAMINE ON ENDOTHELIAL PERMEABILITY AND STRUCTURE AND ADHESION MOLECULES OF THE PARACELLULAR JUNCTIONS OF PERFUSED HUMAN PLACENTAL MICROVESSELS

The microvessels of the human placenta resemble those of skeletal muscle, both in endothelial cell junctional organization and in the single passage extraction of radiolabeled tracers. Addition of histamine (100 mu M) to the fetal perfusate in an isolated term lobule resulted in a rapid and sustained rise (40-80%) over a 30-min perfusion period in the single circulation extraction values of Co-57-labeled cyanocobalamin and of Cr-51-labeled EDTA, but not of Na-22. Extraction values for I-125-albumin were not increased in histamine-perfused vessels nor was any focal leakage of label observed in serial cryostat sections of lobules perfused with rhodamine-conjugated albumin. There was no electron microscopic evidence of transendothelial channels in the microvascular bed; no gaps were seen at the paracellular cleft regions or in neighboring cytoplasm in any microvessels. Tilting of sections on a goniometric stage showed a significant increase in the separation between adjoining endothelial membrane leaflets at tight junctional regions (from 4.1 to 6.1 nm) although the dimensions of the wide zones remained unchanged. Placental microvessels contain the endothelial adhesion molecules PECAM-1 and VE-cadherin in the wide regions of paracellular clefts; PECAM-1 is also localized on the luminal membrane. Histamine-stimulated microvessels showed an altered staining pattern for both of these molecules, at the expense of the cleft regions. These changes in adhesion molecule distribution and tight junctional membrane separation may be parts of a series of events which leads to increased permeability during inflammatory events. (C) 1995 Academic Press, Inc.