ADAM9 is present at endothelial cell - cell junctions and regulates monocyte - endothelial transmigration

We have found that A Disintegrin And Metalloproteinase-9 (ADAM9) localises to cell-cell junctions with VE-Cadherin in confluent endothelial monolayers. Co-cultures of cells separately transfected with ADAM9-EGFP or ADAM9-HA showed expression is required in two adjacent cells for localisation to cell cell junctions suggesting the ADAM9 ectodomain may self-associate. A direct interaction between ADAM9 ectodomains was confirmed using recombinant proteins and an ELISA based method. As the ADAM9 ectodomain can also exist as a soluble form physiologically, we examined if this could inhibit endothelial functions dependent on cell-cell junctions. The soluble ADAM9 ectodomain could not increase endothelial monolayer permeability or inhibit monocyte-endothelial adhesion, but could inhibit monocyte-endothelial transmigration. These novel findings point to ADAM9 playing an important role in endothelial cell biology that is distinct from the other ADAMs. (C) 2017 The Authors. Published by Elsevier Inc.