It takes a spleen to mend a broken heart – that's the conclusion of a surprising new report from researchers at the Massachusetts General Hospital (MGH) Center for Systems Biology, directed by Ralph Weissleder, MD, PhD.
In the July 31 issue of Science the team reports how, in following up an intriguing observation, they discovered an unexpected reservoir of the immune cells called monocytes in the spleen and went on to show that these cells are essential to recovery of cardiac tissue in an animal heart attack model.
"Monocytes are known to serve as a central defense system against injury, and we found that monocytes released from the spleen go directly to the injured heart and participate in wound healing," says Matthias Nahrendorf, MD, PhD, a co-lead author of the study.
Monocytes are generated in the bone marrow, released into the blood and are known to accumulate at injured or infected tissues, where they differentiate into macrophages or dendritic cells. In investigating processes involved in the healing of ischemic heart tissue – the sort of injury produced in a heart attack – in mice, the research team was surprised to find more monocytes accumulating at the site of injury than would be found in the animals' entire circulatory system. When they searched many types of tissue for the presence of cells with monocyte-specific molecules, they only found significant numbers of such cells in the spleen.
Monocytes in the spleen were identical in appearance, composition and function to monocytes in the blood. To investigate the splenic monocyte reservoir's potential involvement in cardiac healing, the researchers used several new technologies. A newly developed microscopic technique allowed them to determine how and where monocytes are stored in the spleen – previously known to store red blood cells – and to study how monocytes are released in response to an experimentally-induced heart attack. A novel three-dimensional optical imaging technique (fluorescence molecular tomography, developed at the MGH Center for Molecular Imaging Research) allowed study of monocyte-mediated immune functions at the site of heart muscle injury.
In mice whose spleens were removed and replaced with a donor organ, an induced heart attack led to rapid increase of spleen-derived donor monocytes in the bloodstream and massive accumulation of donor cells at the site of injury. In animals from whom spleens were removed but not replaced, heart attack produced no significant monocyte increase in the bloodstream or in the heart. "With all these approaches together, we found that the monocytes that travel to the heart after a heart attack come directly from the spleen and that, without the splenic monocytes, the heart tissue does not heal well," says Filip Swirski, PhD, co-lead author of the Science report.
The investigators also found that the hormone angiotensin II, known to be released in response to a heart attack, is actively involved in the release of monocytes from the spleen. Identifying that pathway could lead to ways of manipulating the splenic monocyte reservoir to improve healing after a heart attack and potentially regulate other inflammatory situations. "We need to know whether this monocyte reservoir is important in other diseases – such as viral or bacterial infection, cancer or atherosclerosis – and understand how to precisely control storage and release of monocytes in a therapeutic setting, both of which we are currently investigating," says Mikael Pittet, PhD, senior author of the Science report.
Pittet and Nahrendorf are both assistant professors of Radiology at Harvard Medical School, and Swirski is an instructor in Radiology. Additional co-authors of the Science report are Martin Etzrodt, Moritz Wildgruber, Virna Cortez-Retamozo, Peter Panizzi, PhD, Jose-Luiz Figueiredo, MD, Rainer Kohler, PhD, Aleksey Chudnovskiy, Peter Waterman, Elena Aikawa, MD, PhD, Thorsten Mempel, MD, PhD, and Ralph Weissleder, MD, PhD, MGH Center for Systems Biology; and Peter Libby, MD, Brigham and Women's Hospital. The study was supported by grants from the National Institutes of Health and the MGH Center for Systems Biology.
Massachusetts General Hospital, 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 $500 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 photomedicine.
Sue McGreevey | EurekAlert!
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration
"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...
Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.
Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
16.01.2017 | Power and Electrical Engineering
16.01.2017 | Information Technology
16.01.2017 | Power and Electrical Engineering