Peroxide perturbations
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《细胞学杂志》
Injury triggers invasion of white blood cells into tissues. According to new results from Ji et al. (page 173), PECAM-1, an adhesion molecule on the endothelial cells (ECs) that line blood vessels, does double duty in this invasion process. Direct ligation of PECAM-1 is known to allow neutrophils to crawl between ECs. But, independent of this function in white cell invasion, PECAM-1 is now shown to activate an EC current that may prime cells by loosening their connections.
The messenger that triggers this current is the reactive oxygen species hydrogen peroxide (H2O2). Neutrophil-produced H2O2 signals increase the EC permeability by inducing cell depolarization and an increase in cytosolic Ca2+ concentration, but the mechanism behind these changes remained unknown.
Now, Ji et al. demonstrate that PECAM-1 is required to activate a nonselective cation channel in response to oxidants. The cytoplasmic domain of PECAM-1 is sufficient for activation, suggesting that peroxide-induced Ca2+ influx produced during transmigration does not require PECAM-1 binding between neutrophils and ECs. Phosphorylation of tyrosine residues in this domain is required for the H2O2-induced current, and probably allows interaction with other linker or channel proteins.
Although it is not known which channel is activated, inhibitor studies indicate that the calcium is coming from outside the cell, and not by activation of internal stores. The group plans to investigate the function of the PECAM-1–regulated channel from examining pathological responses in PECAM-1 knock-out mice.
H2O2 and PECAM-1 work together to open a channel.(H2O2 and PECAM-1 work together to open a)
The messenger that triggers this current is the reactive oxygen species hydrogen peroxide (H2O2). Neutrophil-produced H2O2 signals increase the EC permeability by inducing cell depolarization and an increase in cytosolic Ca2+ concentration, but the mechanism behind these changes remained unknown.
Now, Ji et al. demonstrate that PECAM-1 is required to activate a nonselective cation channel in response to oxidants. The cytoplasmic domain of PECAM-1 is sufficient for activation, suggesting that peroxide-induced Ca2+ influx produced during transmigration does not require PECAM-1 binding between neutrophils and ECs. Phosphorylation of tyrosine residues in this domain is required for the H2O2-induced current, and probably allows interaction with other linker or channel proteins.
Although it is not known which channel is activated, inhibitor studies indicate that the calcium is coming from outside the cell, and not by activation of internal stores. The group plans to investigate the function of the PECAM-1–regulated channel from examining pathological responses in PECAM-1 knock-out mice.
H2O2 and PECAM-1 work together to open a channel.(H2O2 and PECAM-1 work together to open a)