| First Author | Abdala-Valencia H | Year | 2018 |
| Journal | J Leukoc Biol | Volume | 104 |
| Issue | 1 | Pages | 215-228 |
| PubMed ID | 29889984 | Mgi Jnum | J:263538 |
| Mgi Id | MGI:6188334 | Doi | 10.1002/JLB.2MA1117-427RR |
| Citation | Abdala-Valencia H, et al. (2018) VCAM-1 induces signals that stimulate ZO-1 serine phosphorylation and reduces ZO-1 localization at lung endothelial cell junctions. J Leukoc Biol 104(1):215-228 |
| abstractText | Endothelial cell VCAM-1 regulates recruitment of lymphocytes, eosinophils, mast cells, or dendritic cells during allergic inflammation. In this report, we demonstrated that, during allergic lung responses, there was reduced zonula occludens (ZO)-1 localization in lung endothelial cell junctions, whereas there was increased lung endothelial cell expression of VCAM-1, N-cadherin, and angiomotin. In vitro, leukocyte binding to VCAM-1 reduced ZO-1 in endothelial cell junctions. Using primary human endothelial cells and mouse endothelial cell lines, Ab crosslinking of VCAM-1 increased serine phosphorylation of ZO-1 and induced dissociation of ZO-1 from endothelial cell junctions, demonstrating that VCAM-1 regulates ZO-1. Moreover, VCAM-1 induction of ZO-1 phosphorylation and loss of ZO-1 localization at cell junctions was blocked by inhibition of VCAM-1 intracellular signals that regulate leukocyte transendothelial migration, including NOX2, PKCalpha, and PTP1B. Furthermore, exogenous addition of the VCAM-1 signaling intermediate H2 O2 (1 muM) stimulated PKCalpha-dependent and PTP1B-dependent serine phosphorylation of ZO-1 and loss of ZO-1 from junctions. Overexpression of ZO-1 blocked leukocyte transendothelial migration. In summary, leukocyte binding to VCAM-1 induces signals that stimulated ZO-1 serine phosphorylation and reduced ZO-1 localization at endothelial cell junctions during leukocyte transendothelial migration. |
