Immune cells produce chemical messenger that prevents heart disease-
related inflammation

Date:
March 29, 2022
Source:
Massachusetts General Hospital
Summary:
In the bone marrow, B cells produce a chemical messenger called
acetylcholine that prevents inflammation in the heart and blood
vessels by blocking white blood cell production. Tapping into this
process may help scientists target inflammation in cardiovascular
conditions.



FULL STORY ==========================================================================
The immune system's white blood cells, which are produced in the bone
marrow, mostly help to defend against bacteria and injury, but sometimes
they can turn against the body -- for example, in cardiovascular
disease, their inflammatory aggression can harm arteries and the
heart. New research in Nature Immunologythat was led by investigators at Massachusetts General Hospital (MGH) provides insights into the pathways
that increase or decrease the bone marrow's output of these cells. The
findings may lead to new treatments for conditions that arise when the
balance of white blood cell production goes awry.


========================================================================== Senior author Matthias Nahrendorf, MD, PhD, an investigator in MGH's
Center for Systems Biology and The Richard Moerschner professor at the MGH Research Institute and Harvard Medical School, explains that the nervous
system plays a role in controlling blood cell production through chemical messengers or neurotransmitters. "This is for instance important in people exposed to stress, where stress hormones -- part of the 'fight-or-flight' response controlled by the sympathetic nervous system -- may increase
bone marrow activity and cardiovascular inflammation in response to
the neurotransmitter noradrenaline," he says. The sympathetic nerves
have a counter player -- the parasympathetic nerves, which slow down
responses and bring about a state of calm to the body, mainly through
the neurotransmitter acetylcholine.

Because acetylcholine can have a protective effect against inflammation
and heart disease, the researchers studied this neurotransmitter in
the bone marrow. "When we looked into how acetylcholine acts on the
production of blood cells, we found that it does the expected -- it
reduces white blood cells, as opposed to noradrenaline, which increases
them," says Nahrendorf. "What was unexpected though was the source of
the neurotransmitter acetylcholine." The team found no evidence in
the bone marrow of the typical nerve fibers that are known to release acetylcholine. Instead, B cells, which are themselves a type of white
blood cell (most known for making antibodies), supplied the acetylcholine
in the bone marrow. "Thus, B cells counter inflammation -- even in the
heart and the arteries -- via dampening white blood cell production in
the bone marrow. Surprisingly, they use a neurotransmitter to do so,"
says Nahrendorf.

Tapping into this process may help investigators develop strategies
to block inflammation in cardiovascular conditions such as
atherosclerosis. "Ultimately this may lead to new therapeutics that
combat myocardial infarction, stroke, and heart failure," says Nahrendorf.

Additional study authors include Maximilian J. Schloss, Maarten Hulsmans,
David Rohde, I-Hsiu Lee, Nicolas Severe, Brody H. Foy, Fadi E. Pulous,
Shuang Zhang, Konstantinos D. Kokkaliaris, Vanessa Frodermann, Gabriel Courties, Chongbo Yang, Yoshiko Iwamoto, Anders Steen Knudsen, Cameron
S. McAlpine, Masahiro Yamazoe, Stephen P. Schmidt, Gregory R. Wojtkiewicz, Gustavo Santos Masson, Karin Gustafsson, Diane Capen, Dennis Brown,
John M. Higgins, David T. Scadden, Peter Libby, Filip K. Swirski, and
Kamila Naxerova.

This work was supported in part by the National Heart Lung and Blood
Institute at the National Institutes of Health (grant HL142494) and the
MGH Research Scholar program.


========================================================================== Story Source: Materials provided by Massachusetts_General_Hospital. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Maximilian J. Schloss, Maarten Hulsmans, David Rohde, I-Hsiu Lee,
Nicolas
Severe, Brody H. Foy, Fadi E. Pulous, Shuang Zhang, Konstantinos D.

Kokkaliaris, Vanessa Frodermann, Gabriel Courties, Chongbo Yang,
Yoshiko Iwamoto, Anders Steen Knudsen, Cameron S. McAlpine, Masahiro
Yamazoe, Stephen P. Schmidt, Gregory R. Wojtkiewicz, Gustavo
Santos Masson, Karin Gustafsson, Diane Capen, Dennis Brown, John
M. Higgins, David T. Scadden, Peter Libby, Filip K. Swirski, Kamila
Naxerova, Matthias Nahrendorf. B lymphocyte-derived acetylcholine
limits steady-state and emergency hematopoiesis. Nature Immunology,
2022; DOI: 10.1038/s41590-022-01165-7 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220329185445.htm

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