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면역세포 신호전달 메커니즘 밝혀졌다

2005. 09. 22, am 11:18 (KST) 기사전달 기사프린트 기사저장



면역세포들은 나노튜브 터널망을 통해 서로 신호를 신속히 교환한다는 사실이 밝혀졌다.

미국 피츠버그 대학 의과대학 면역학교수 러셀 솔터 박사는 사이먼 워트킨스 박사와 함께 의학전문지 '면역(Immunity)' 9월호에 발표한 연구논문에서 항원전달 면역세포인 수지상(樹枝狀)세포와 대식(大食)세포가 나노튜브 터널망을 통해 수 백 나노미터까지 멀리 떨어진 면역세포들에 칼슘 등 분자메시지를 불과 몇 초만에 전달한다는 사실을 알아냈다고 밝혔다.

이 나노튜브 터널은 너비가 사람 머리카락보다 5천 배나 작은 35-200나노미터(1나노미터는 10억분의 1m)이며 길이가 각기 다른 이러한 통신망을 한번에 최고 75개까지 가질 수 있다고 솔터 박사는 밝혔다.

이는 우리 몸의 면역반응이 그토록 신속하고 정확한 이유를 설명해 주는 것이라고 솔터 박사는 지적했다.
이는 또 뉴런(신경세포)이외의 세포도 자체의 정보교환 메커니즘을 통해 장거리통신을 할 수 있는 능력이 있다는 사실을 보여주는 것이다.

솔터 박사는 앞으로 연구를 더 계속하면 면역세포가 이 나노통신망을 이용, 항원을 다른 면역세포들에 전달해 염증반응을 일으키는 과정을 알아낼 수 있을 것이라고 말했다.

이러한 마이크로 통신망을 가진 다른 형태의 세포도 있을 수 있을 것이라고 솔터 박사는 덧붙였다.

(피츠버그 UPI=연합뉴스)


Source:
http://www.scienceblog.com/cms/underground_tunnels_help_immune_cells_chat_8991



'Underground' tunnels help immune cells chat

Immune system cells are connected to each other by an extensive network of
tiny tunnels that, like a building's hidden pneumatic tube system, are
used to shoot signals to distant cells. This surprising discovery, being
reported by two University of Pittsburgh School of Medicine researchers in
the September issue of the journal Immunity, may explain how an immune
response can be so exquisitely swift. The research not only proves cells
other than neurons are capable of long-distance communication, but it
reveals a hereto-unknown mechanism cells use for exchanging information.

Blood-derived dendritic cells and macrophages, both antigen-presenting
cells, make use of these so-called tunneling nanotubules to relay
molecular messages, report Simon C. Watkins, Ph.D., and Russell D. Salter,
Ph.D. Further research may show there are additional cell types with these
microscopic tunnel connections. Thus far, their studies suggest the
tunnels do not exist between commonly used fibroblast and tumor cell lines.

Interestingly, if not for a minor mishap while carrying out an experiment,
the authors might not have discovered the existence of these physical
structures and conducted the studies that revealed their role in
intercellular communication.

Using a custom-built, multi-camera live cell microscopic imaging system,
they report that, in a matter of seconds, dendritic cells and macrophages
can send waves of calcium and other small molecules to cells hundreds of
micrometers away. Each nanotubule measures between 35 and 200 nanometers
across ? 5000 times smaller than the width of a human hair ? and at any
given time, cells may have up to 75 of these extensions, each of varying
lengths.

"Considering their scale, these nanotubules are allowing communication
between fairly distant cells. If instead of a culture dish we were talking
about a large metropolitan area, the distance would be about the
equivalent to four or five city blocks. That's nothing short of amazing,"
remarked Dr. Salter, associate professor of immunology at the University
of Pittsburgh School of Medicine.

The authors are the first to explain the function of tunneling
nanotubules, structures that were first described in fruit flies in 1998,
and subsequently, identified in a handful of different types of animal and
human cells.

"It's one thing to find that this intricate physical network exists but
quite astonishing to learn that immune system cells are using it to relay
molecular signals to one another," said Dr. Watkins, professor and vice
chair, department of cell biology and physiology, and director of the
Center for Biologic Imaging, University of Pittsburgh School of Medicine.

While gap junctions - interconnecting molecular bridges that conjoin
tightly packed cells - are known to generate calcium signals and transport
other molecules between cells, the researchers say the tunneling
nanotubules are something quite different.

"This is clearly a third form of intercellular communication, distinct
from gap junctions and synapses used by nerve cells. And, it is possible
that tunneling nanotubules are essential for the function of the immune
system, just as gap junctions are critical for the function of cardiac
muscle. Exactly how this is so, we don't know," added Dr. Watkins, who
also is a professor of immunology.

"Further study may help us better understand how they're involved in the
local inflammatory response of the immune system. For instance, we may
find that dendritic cells use this network to distribute antigens to other
cells and it may be conceivable to follow the entire pathway by tracing
the network of tunneling nanotubules," said Dr. Salter.

The authors' discovery builds on their recent research showing how
dendritic cells respond to stimuli, but, as they freely admit in this
paper, it was due in large part to an accidental observation, that giving
just the slightest poke to a single cell can set off a chain reaction
whereby cell after cell discharges bursts of calcium.

In their earlier studies, they described how dendritic cells unfurl hidden
veils ? membranes that are so thin they can barely be imaged ? and use
these veils to move in on and capture their target. In the presence of E.
coli, this occurs so rapidly and with such vigor that in accelerated
time-lapse video, the cells appear more like a pack of wild animals
feeding on a carcass.

But two things baffled the researchers. Dendritic cells extended their
veils even before making physical contact with E. coli, yet macrophages,
cells not normally picky about the antigens they engulf, were completely
unresponsive to the bacteria. In order to understand how dendritic cells
first sense the presence of an antigen and why the reaction is
cell-specific, the authors decided to look at calcium flux, a
well-recognized early measure of stimulation in numerous cell types. The
use of a fluorescent dye, which allows direct measurement of calcium
levels, would determine if calcium flux occurs before dendritic cells
unfurl their veils.

With a microinjection tip, they squirted a mixture of E. coli fragments
into a culture dish, and, indeed, one to two minutes before the appearance
of the thin membranes, there were bursts of color indicative of calcium
flux. Given their earlier results, the researchers anticipated that by
repeating the experiment with macrophages there'd be no response. But as
luck would have it, the microscopic bacteria sample somehow got clogged
inside the tip, and before Dr. Watkins realized the need to pull away from
the cell, he had already given it a jab.

"On the screen it looked like flash bulbs going off in a dark concert
arena," Dr. Salter recalled of that moment, when to both their great
surprise the researchers witnessed how that little mishap had caused the
macrophages to release bursts of calcium.

Returning to dendritic cells, they found that by giving a deliberate poke
with an empty microinjection tip it caused the same reaction. But why some
cells responded and others did not made Drs. Salter and Watkins wonder if
there was some sort of physical structure connecting only those cells that
discharged. A literature search turned up a handful of papers describing
tunneling nanotubules, and further imaging using the highest magnification
possible disclosed their presence in both the dendritic cells and
macrophages.

In their most definitive experiment, the researchers placed dendritic
cells, macrophages and a small amount of the E. coli mixture in the same
culture dish. The dendritic cells, as would be expected, fluxed calcium in
response to the E. coli. But a few seconds later, calcium could also be
seen shooting through the tiny tunnels extending from dendritic cells to
neighboring macrophages.

"This may solve some of the mystery of how a local stimulus directed at a
very small number of cells can be amplified and result in a successful
immune response," explained Dr. Watkins.

"Quite possibly, the tunneling nanotubules enable a small number of
dendritic cells with captured antigens to reach other dendritic cells in
lymph nodes, increasing the number of these cells capable of stimulating T
lymphocytes," added Dr. Salter.

The finding that nanotubules play a role in sending molecular signals to
other immune system cells calls into question the long-held belief that
immune system cells talk to one another solely by secreting substances
such as cytokines, the authors say. It now seems clear that intercellular
communication is much more complicated. While it would be fascinating to
see this interplay inside living tissue, detecting the tiny tubules in
such a complex environment may be nearly impossible with current
technology.

From University of Pittsburgh Medical Center

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Submitted by BJS on Mon, 2005-10-03 08:45.

joannax13 | Mon, 2005-10-03 15:52


Copyright 2005, Science Blog.
Staring directly at the Sun, so you don't have to.
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On the contrary, let us embrace Science and the new technologies
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