The role of integrins in the maintenance of endothelial monolayer integrity.

Abstract

Abstract. This paper shows that, in confluent human umbilical vein endothelial cell (EC) monolayers, the integrin heterodimers c~2/3~ and ot5/3~, but not other members of the/3~ subfamily, are located at cell-cell contact borders and not at cellular free edges. Also the cry chain, but not its most common partner/33, that is widely expressed in EC cell-matrix junctions, is found at cell-cell borders. In EC monolayers, the putative ligands of oe2/3~ and o~5/3t receptors, i.e., laminin, collagen type IV, and fibronectin, are also organized in strands corresponding to cell-cell borders. The location of the above integrin receptors is not an artifact of in vitro culture since it has been noted also in explanted islets of the native umbilical vein endothelium. The integrins tx2~ and ot5/3~ play a role in the maintenance of endothelial monolayer continuity in vitro. Indeed, specific antibodies to ot2#~, ot5/3~, and the synthetic peptide GRGDSP alter its continuity without any initial cell detachment. Moreover, antibodies to oLs/3~ increase the permeation of macromolecules across confluent EC monolayers. In contrast/33 antibodies were ineffective. It is suggested that the relocation of integrins to cell-cell borders is a feature of cells programmed to form polarized monolayers since integrins have a different distribution in nonpolar confluent dermal fibroblasts. The conclusion is that some members of the integrin superfamily collaborate with other intercellular molecules to form lateral junctions and to control both the monolayer integrity and the permeability properties of the vascular endothelial lining. This also suggests that integrins are adhesion molecules provided with a unique biochemical adaptability to different biological functions.

The integrin coactivator Kindlin-2 plays a critical role in angiogenesis in mice and zebrafish

“…Direct evidence that underscores the physiologic significance of integrin-matrix interactions in vascular integrity comes from the studies showing that disruption of integrin-ECM interaction with RGD peptides increases venular permeability by 2-to 3-fold in vivo 43 and reduces the barrier properties of endothelial monolayers. 44 In mature EC cultures, ␣V␤3 also localizes to and maintains the integrity of the junctions 45 and decreased ␤3 expression with siRNA increases permeability. 46 Mechanistically, it has been suggested that this integrin collaborates with other intercellular molecules to form lateral junctions and specifically participates in formation of adherens junctions.…”

Role of the extracellular matrix in age-related modifications of the rat aorta. Ultrastructural, morphometric, and enzymatic evaluations.

“…Endothelial lining integrity is achieved by the presence of tight, adherent, and gap junctions between cells 21 and by surface integrins such as a2/31 or a5/31, whereas extracellular matrix proteins such as fibronectin or laminin do not seem to significantly interfere. 22 Because it has been demonstrated that integrins are mainly distributed at cell-cell contacts, a reduction in the surface area available for cell-cell interactions might greatly contribute to the fragility of the endothelial lining. In both adult and old animals, moreover, the subintimal space is bigger, sometimes swollen, and generally rich in glycosaminoglycans (visualized as toluidine blue-stained precipitates), 11 which might alter the permeability and the behavior of the intima components.…”

Induction of IL-6 expression by mechanical stress in the trabecular meshwork

“…Effects of IL-6 on SC cell monolayer permeability were measured using the method described by Langeler and van Hinsbergh [33], and modified by Lampugnani et al [34]. Briefly, SC primary cultures at passage 3 were grown in Transwell cell culture chambers (0.4 μm pore size, polyester filters, from Corning Life Sciences, Acton, MA) for at least 2 weeks.…”