Browse by Medical Category
Monday, August 30, 2010
Ability to gently collect neutrophils may improve understanding of immune response to serious injury
A team led by Massachusetts General
Hospital (MGH) scientists has developed a new microfluidic tool for quickly and
accurately isolating neutrophils -- the most abundant type of white blood cell --
from small blood samples, an accomplishment that could provide information
essential to better understanding the immune system's
response to traumatic injury. The
system, described in a Nature Medicine
paper that received advance online release, also can be adapted to isolate
almost any type of cell.
"Neutrophils are currently
garnering a lot of interest from researchers and clinicians, but collecting and
processing them has been a real challenge," says Kenneth Kotz, PhD, of the
MGH Center for Engineering in Medicine, lead
author of the study. "This tool
will allow a new range of studies and diagnostics based on cell-specific genomic
and proteomic signatures."
Part of the body's first-line defense against injury or infection,
neutrophils were long thought to play fairly simple roles, such as releasing
antimicrobial proteins and ingesting pathogens.
But recent studies find their actions to be more complex and critical to
both chronic and acute inflammation, particularly the activation of the immune
system in response to injury.
Studying patterns of gene
expression and protein synthesis in neutrophils could reveal essential
information about the immune response, but gathering the cells for analysis has
been challenging. Standard isolation
procedures take more than two hours and require relatively large blood
samples. Neutrophils also are sensitive
to handling and easily become activated, changing the molecular patterns of
interest, and they contain very small amounts of messenger RNA, which is required
for studies of gene expression.
Building on their experience
developing silicon-chip-based devices that capture CD4 T cells for HIV
diagnosis or isolate circulating tumor cells, Kotz's
team developed a system that gathers a neutrophil-rich sample from microliter-sized
blood samples in less than 5 minutes, reducing the risk of disturbing cells in
the process. To meet the requirements
for speed and precision, the researchers completely redesigned the geometry,
antibody-based coating and other aspects of the cell-capture module at the
heart of the device. The samples
collected were successful in revealing differences in gene and protein activity
relevant to the cells' activation
While the laboratory tests were
encouraging, samples from critically injured patients need to be handled and
processed in real-world clinical environments.
Through the efforts of study co-author Lyle Moldawer, PhD, of the University
of Florida College of Medicine, the devices were tested at six additional sites
participating in a major national study of the immune response to injury. Analyzing samples from 26 patients with serious
burns or other traumatic injuries revealed complex gene expression patterns
that shifted during the 28 days after injury, probably reflecting complex
interactions between various immune system components.
Ronald Tompkins, MD, ScD -- chief
of the MGH Burns Service, a study co-author and principal investigator of the
"Inflammation and the Host Response to Injury" initiative -- says, "This
technology has been widely implemented in our 'Glue
Grant Program,' with a major
impact. The ability to capture specific
cells in a routine clinical environment rapidly and accurately offers a
possible change in the paradigm of normal clinical diagnostics." The Nature Medicine study is part of the
National-Institute-of-Health-funded, large-scale collaborative research program
and involved its seven clinical sites and seventeen academic institutes across
the United States.
Kotz says, "Until now, it's been logistically impossible to study neutrophils
to the extent we have in this paper." He notes that their analysis of neutrophil
samples from trauma patients is the largest such investigation to date and
adds, "This technology -- which is much faster and gentler than current
approaches to isolating cells -- can be scaled and modified to capture just
about any cell type, and we're
working to apply it to other cell-based assays."
Mehmet Toner, PhD, director of the BioMEMS Resource
Center in the MGH Center
for Engineering in Medicine, is senior author of the Nature Medicine article. In
addition to Tompkins and Moldawer, primary co-authors are Aman Russom, Alan
Rosenbach, Jeremy Goverman, Shawn Fagan and Daniel Irimia, MGH; Wenzong Xiao,
Weihong Xu, Julie Wilhelmy, Michael Mindrinos, and Ronald Davis, Stanford
Genome Technology Center; Carol Miller-Graziano, Asit De and Paul Bankey,
University of Rochester School of Medicine; Wei-Jun Qian, Brianne Petritis,
David Camp, and Richard Smith, Pacific Northwest National Laboratory; Elizabeth
Warner, University of Florida College of Medicine; and Bernard Brownstein,
Washington University of St. Louis.
established in 1811, is the original and largest teaching hospital of Harvard Medical School.
The MGH conducts the largest hospital-based research program in the United States,
with an annual research budget of more than $600 million and major research
centers in AIDS, cardiovascular research, cancer, computational and integrative
biology, cutaneous biology, human genetics, medical imaging, neurodegenerative
disorders, regenerative medicine, systems biology, transplantation biology and
Sue McGreevey, 617 724-2764, firstname.lastname@example.org
Back to Top