The neutrophil as firefighter

entrosomes are required for cytokinesis and are important in cell cycle progression—but how are centrosomes connected to these essential cellular functions at the molecular level? On page 535, Gromley et al. describe the maternal cen-triole protein centriolin, the first integral centrosome protein linked to both cytokinesis and cell cycle progression in vertebrate cells. Overexpression, siRNA silencing, or antibody inhibition of centriolin causes an unusual cytokinesis defect, in which cells remain connected by long strands of cytoplasm and form syncytia. Some of the cells later undergo cell cycle arrest in G1/G0, and some undergo apoptosis. The cytokinesis defect is caused by a domain in centriolin that shares homology with yeast regulatory proteins in the MEN/SIN pathway, which controls yeast mitotic exit and cytokinesis. The results suggest that centriolin links centrosomes to a critical cytokinesis regulatory system and possibly to a cell cycle checkpoint. Screening work is now uncovering additional members of the cytokinesis pathway. Centriolin also contains domains with homology to proteins implicated in human tumorigenesis. Since centrosome defects would cause aneuploidy, a hallmark of cancer, the authors are now trying to determine whether centriolin has oncogenic functions. ᭿ C Centriolin deficiency disrupts cytokinesis. The neutrophil as firefighter evere bacterial infection or trauma frequently leads to a systemic inflammatory response, a self-reinforcing activation of neutrophils and vascular endothelial cells that can be deadly. On page 641, Cepinskas et al. describe a neutrophil-mediated signaling mechanism that inhibits inflammation. The findings demonstrate a novel function for neutrophils and a previously unknown form of immunological tolerance, and they identify a promising target for new anti-inflammatory drugs. In systemic inflammation, circulating cytokines cause the transcription factor NF ␬ B to translocate from the cytoplasm to the nucleus of vascular endothelial cells, where it induces the transcription of pro-inflammatory genes. Using a cell culture model of inflammation, the authors found that the migration of neutrophils across a monolayer of cytokine-activated endothelial cells causes NF ␬ B levels in the endothelial cell nuclei to drop. Cross-linking the adhesion molecule S Breaking down barriers n page 653, Nitta et al. show that removal of the tight junction component claudin-5 makes the murine blood–brain barrier (BBB) selectively permeable to small molecules. Although considerably more work is needed before this approach can be applied clinically, the finding could be a boon for drug delivery to the central nervous system. Although it was first described over a century ago, it has …