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

This Article PDF (Full Text) 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 Google Scholar Articles by Leslie, M. PubMed Articles by Leslie, M. Social Bookmarking                      What's this?

A macrophage grabs but does not swallow a human red blood cell (arrow) carrying CD47.

Like a well-trained police dog, a macrophage responds to a signal that means "let go." Tsai and Discher reveal that the signal works by blocking a molecular motor that helps drag bacteria and other potential enemies into the macrophage.

Macrophages sweep up pathogens while leaving our own cells alone. A two-step procedure for recognizing intruders helps avoid misdirected attacks. In the first step, macrophages snare and begin swallowing objects studded with IgG antibodies, which usually latch onto interlopers. But the antibodies are sloppy, sometimes attaching to the body's own cells. So before a macrophage engulfs its target, it also checks for a second form of identification, the protein CD47. If a "self" version of CD47 is present, it induces the macrophage to disengage. How CD47 spurs a macrophage to stop mid-swallow was uncertain.

To find out, Tsai and Discher followed human macrophages as they tangled with human and sheep red blood cells. When a macrophage meets its quarry, actin molecules flock to the contact site and polymerize, extending the cell's membrane around the target. Another protein called nonmuscle myosin also moves in. It contracts to help reel in the partly engulfed object. The researchers found that actin and nonmuscle myosin relocated normally when the macrophages encountered sheep red blood cells, which sport a "foreign" version of CD47. But when the targets were human red blood cells—which carry self CD47—only actin is mobilized.

Further experiments indicated that CD47 exerts its effects through its receptor on macrophages, SIRP, which in turn indirectly inactivates the myosin by preventing the addition of a phosphate group to the brawny molecule. By shutting down a pulling protein needed to complete phagocytosis, the researchers conclude, self CD47 prevents cells that carry it from being eaten. The team speculates that macrophages benefit from the two-step recognition process because it allows them to restrain a potential troublemaker while checking its credentials. As a result, they are poised to gobble the target if it turns out to be a threat.

Reference:

Tsai, R.K., and D.E. Discher. 2008. J. Cell Biol. 180:989–1003.[Abstract/Free Full Text]

Mitch Leslie

mitchleslie{at}comcast.net

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

This Article PDF (Full Text) 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 Google Scholar Articles by Leslie, M. PubMed Articles by Leslie, M. Social Bookmarking                      What's this?