PECAM-1 (CD31) regulates a hydrogen peroxide–activated nonselective cation channel in endothelial cells

Hydrogen peroxide (H2O2) released by neutrophils is an important mediator of endothelial cell (EC) injury and vascular inflammation via its effect on EC-free Ca2+, [Ca2+]i. Although the underlying mechanisms are not well understood, platelet endothelial cell adhesion molecule (PECAM)-1/CD-31 is a critical modulator of neutrophil–EC transmigration. PECAM-1 is also known to regulate EC calcium signals and to undergo selective tyrosine phosphorylation. Here, we report that PECAM-1 molecules transduce EC responses to hydrogen peroxide. In human umbilical vein EC and REN cells (a PECAM-1–negative EC-like cell line) stably transfected with PECAM-1 (RHP), noncytolytic H2O2 exposure (100–200 μM H2O2) activated a calcium-permeant, nonselective cation current, and a transient rise in [Ca2+]i of similar time course. Neither response was observed in untransfected REN cells, and H2O2-evoked cation current was ablated in REN cells transfected with PECAM-1 constructs mutated in the cytoplasmic tyrosine–containing domain. The PECAM-dependent H2O2 current was inhibited by dialysis of anti–PECAM-1 cytoplasmic domain antibodies, required Src family tyrosine kinase activity, was independent of inositol trisphosphate receptor activation, and required only an intact PECAM-1 cytoplasmic domain. PECAM-1–dependent H2O2 currents and associated [Ca2+]i transients may play a significant role in regulating neutrophil–endothelial interaction, as well as in oxidant-mediated endothelial response and injury.

• Publication year

  2002

• Venue

  Journal of Cell Biology

• Publication date

  2002-04-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1083/jcb.200110056PMID 11927609PMCID 2173260
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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