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High-speed images show how cells mobilize for immune response

with the second wave encircling the phagosome or sac-like compartment. This second wave allows the digestive enzymes to enter the phagosome and finally destroy the target.

When Petty introduced a mutation in the gene (FcyRIIA) that controls phagocytosis, he found that the calcium wave simply circled the cell and bypassed the phagosome altogether. As a result, the immune cell could engulf, but could not carry out the destruction of its target. This led him to conclude that the LTL sequence orchestrates the cell signaling process.

The sequence may also have a role in directing other cell activities, for example signaling the endoplasmic reticulum to form a spindle that connects the phagosome and the outer cell membrane. "The spindle seems to act as an extension cord that signals the calcium wave into the phagosome to finish the attack," suggests Petty.

Petty explains that many of these findings are possible thanks to high-speed imaging techniques that enable him to merge knowledge of physics with cell and molecular biology. He uses high sensitivity fluorescence imaging with shutter speeds 600,000 times faster than video frames.

"Before the advent of high-speed imaging, you could not ask many of these questions because we had no way to see the movement of calcium waves," he says. "With conventional imaging you ended up with a blur of calcium." By contrast, Petty's images resemble the movement of a comet across the night sky.

In the study reported in PNAS, Petty used leucocytes as a model for the process. The amino acid sequence is in the region of the gene FcyRIIA. He is currently studying the same phenomena in the eye, where phagocytosis disposes of the regularly-shed remnants of photoreceptor cells.


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Contact: Betsy Nisbet
bsnisbet@umich.edu
734-647-5586
University of Michigan Health System
16-Apr-2003


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