UIC researchers have immune cells running in circles

November 02, 2009

University of Illinois at Chicago College of Medicine researchers have identified the important role a protein plays in the body's first line of defense in directing immune cells called neutrophils toward the site of infection or injury.

Their results are described online in the Proceedings of the National Academy of Sciences.

Neutrophils are white blood cells that are activated by chemical cues to move quickly to the site of injury or infection, where they ingest bacteria. When alerted to infection, neutrophils move by changing shape, developing a distinct front and back, sending a "foot" out in front of them, and "crawling" toward the site of infection.

Hoping to better understand the role of a protein called p55 or MPPI that they had previously identified as highly expressed in neutrophils, the UIC researchers bred the first mice that completely lacked this protein.

The "knockout" mice had marked difficulty fighting infection and were slow to heal, according to Athar Chishti, professor of pharmacology and principal investigator in the study.

Instead of forming a single large pseudopod, or foot-like extension, in the direction of the infection, neutrophils from the knockout mice formed a number of small extensions all around the cell, said Chishti.

Neutrophils lacking p55 would follow a meandering path, wandering in circles. "It was as though the neutrophils had lost their sense of direction," said Brendan Quinn, graduate assistant researcher in pharmacology and first author of the study.

Neutrophils are part of the body's innate immunity and its first line of defense, so the speed of the response is key to healing. "The neutrophils eventually get to the infection site, but they would get there late," Quinn said.

The researchers also established how p55 wields its effect on neutrophils, demonstrating that although the cell's ability to reorganize its actin skeleton to produce pseudopods was undisturbed, a signaling lipid known to be important in establishing polarity, called PIP3, failed to localize on the leading edge of the p55-null neutrophils, instead diffusing throughout the cell.

Further, the p55-null neutrophils had a marked reduced activation of another important signaling protein, Akt, which is believed to play an important role in many cancers.

"This study offers clues to an important cell signaling pathway that is critical to cellular polarization processes in neutrophils and many other cells," said Chishti.
-end-
Emily J. Welch, Anthony C. Kim, Anwar A. Khan and Shafi M Kuchay of the department of pharmacology at the UIC College of Medicine and Mary A. Lokuta and Anna Huttenlocher of the departments of pediatrics and pharmacology at the University of Wisconsin, Madison, also contributed to the study. The work was funded by grants from the National Institutes of Health and the Department of Defense Neurofibromatosis Research Program Career Development Award.

For more information about UIC, visit www.uic.edu.

University of Illinois at Chicago

Related Protein Articles from Brightsurf:

The protein dress of a neuron
New method marks proteins and reveals the receptors in which neurons are dressed

Memory protein
When UC Santa Barbara materials scientist Omar Saleh and graduate student Ian Morgan sought to understand the mechanical behaviors of disordered proteins in the lab, they expected that after being stretched, one particular model protein would snap back instantaneously, like a rubber band.

Diets high in protein, particularly plant protein, linked to lower risk of death
Diets high in protein, particularly plant protein, are associated with a lower risk of death from any cause, finds an analysis of the latest evidence published by The BMJ today.

A new understanding of protein movement
A team of UD engineers has uncovered the role of surface diffusion in protein transport, which could aid biopharmaceutical processing.

A new biotinylation enzyme for analyzing protein-protein interactions
Proteins play roles by interacting with various other proteins. Therefore, interaction analysis is an indispensable technique for studying the function of proteins.

Substituting the next-best protein
Children born with Duchenne muscular dystrophy have a mutation in the X-chromosome gene that would normally code for dystrophin, a protein that provides structural integrity to skeletal muscles.

A direct protein-to-protein binding couples cell survival to cell proliferation
The regulators of apoptosis watch over cell replication and the decision to enter the cell cycle.

A protein that controls inflammation
A study by the research team of Prof. Geert van Loo (VIB-UGent Center for Inflammation Research) has unraveled a critical molecular mechanism behind autoimmune and inflammatory diseases such as rheumatoid arthritis, Crohn's disease, and psoriasis.

Resurrecting ancient protein partners reveals origin of protein regulation
After reconstructing the ancient forms of two cellular proteins, scientists discovered the earliest known instance of a complex form of protein regulation.

Sensing protein wellbeing
The folding state of the proteins in live cells often reflect the cell's general health.

Read More: Protein News and Protein Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.