Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text (PDF, 969K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Social Bookmarking                            What's this?

Mopping up chemokines

Apoptotic cells (right) accumulate CCR5 (top right). BOXER/MACMILLAN

In both Iraq and the immune system, it's not the initial victory but the subsequent cleaning up that is the hardest part. Now, Amiram Ariel, Charles Serhan (Harvard Medical School, Boston, MA), and colleagues show that the mess after an infection is cleared up in part by dying cells.

This very act of cell death—notably of neutrophils and T cells—is one way of actively resolving an inflammatory event. But the signals that first drew immune cells to the site of inflammation also need to be destroyed: chemicals via enzymatic degradation and proteins and peptides by other means. Now, the Boston team shows that some of these chemokine proteins are mopped up by apoptotic cells. These dying cells turn up expression of their CCR5 chemokine receptors even as the cells are about to be engulfed by macrophages.

CCR5 is important because it binds several key chemokines—"the lion's share of the chemokines at a site of inflammation," says Serhan. "So you need a good mechanism to explain their clearance."

Late apoptotic cells had higher CCR5 staining; this was reduced by a proinflammatory cytokine but increased by proresolution mediators. The result was more chemokine binding to late apoptotic cells. If CCR5 was knocked out or antagonized, however, fluid from resolving infections had higher chemokine levels.

Thus it appears that the dying cells are mopping up chemokines and taking them to the grave. "It sounds almost too simple," says Serhan, but he doesn't think this is his "Mission Accomplished." Rather it is a reminder, he says, that "when cells go through apoptosis they don't stop signaling."

Reference:

Ariel, A., et al. 2006. Nat. Immunol. doi:10.1038/ni1392.

William A. Wells

wellsw{at}rockefeller.edu

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This Article Full Text (PDF, 969K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Social Bookmarking                            What's this?