Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists first to see trafficking of immune cells in beating heart

12.07.2012
Blood flow to the heart often is interrupted during a heart attack or cardiac surgery. But when blood flow resumes, the heart may still falter. That's because collateral damage can occur as blood re-enters the heart, potentially slowing recovery and causing future cardiac troubles.

Researchers investigating this type of secondary heart damage have been stymied by the inability to see in real time how restoring blood flow leads to inflammation that can cause further injury.


Working in mice, scientists at Washington University School of Medicine in St. Louis have used two-photon imaging to capture the first images of a beating heart at a resolution so detailed they can track individual immune cells swarming into the heart, causing inflammation. These immune cells, shown in green, are moving from the blood vessels in the heart into the heart muscle. Credit: Washington University in St. Louis

Now, working in mice, surgeons and scientists at Washington University School of Medicine in St. Louis, have captured the first images of a beating heart at a resolution so detailed they can track individual immune cells swarming into the heart muscle, causing inflammation.

The achievement is detailed in the July issue of the Journal of Clinical Investigation.

The researchers say that the imaging technique, called intravital two-photon imaging, is a powerful tool for understanding the inflammation that occurs when blood flow to the heart is temporarily stopped and later restarted.

"Inflammation is quite common after a heart attack, open-heart surgery, heart transplants and in atherosclerosis, and it can severely hamper recovery and lead to death," says senior author Daniel Kreisel, MD, PhD, a Washington University cardiothoracic surgeon who operates at Barnes-Jewish Hospital. "But little is known about how inflammation ramps up in the heart. Now that we have the ability to see all the cellular players involved, we can begin to think about new therapeutic targets for treatment."

Two-photon imaging has been used to image other organs in living mice but never the heart. Scientists had assumed that the flutter of the beating heart, which pulses about 500 times a minute in a mouse, would blur any images of individual cells.

"No one thought we could get clear images of cells inside the beating heart," says Wenjun Li, MD, research instructor of surgery and co-lead author with Ruben Nava, MD, and Alejandro Bribriesco, MD, both surgical residents at Barnes-Jewish Hospital. "But the images we captured are incredibly rich in detail, right down to the level of single cells. We think the principles underlying inflammation in the mouse heart will be applicable to humans."

One advantage of two-photon microscopy is the ability to penetrate deep into tissue, allowing scientists to image cells in the heart tissue.

Using the technique in mice that had undergone heart transplants or had a blood flow to the heart temporarily interrupted, the researchers saw that within minutes of restoring blood flow, specialized white blood cells, called neutrophils, rushed into the heart. (To see a video of neutrophils, shown in green, swarming into the beating heart of a mouse after a heart transplant, click here.)

Neutrophils are known to be a key driver of inflammation but scientists had never seen the trafficking of immune cells as they move from the circulation into the heart muscle, where the cells formed large clusters that cause tissue damage.

In addition, by blocking neutrophils from blood vessel walls, the researchers could markedly reduce the movement of these cells into the heart, preventing further injury.

Kreisel, Li and their colleagues collaborated with co-senior author Mark Miller, PhD, an assistant professor of pathology and immunology, who pioneered the use of two-photon microscopy for studying the trafficking of white blood cells in living mice. Together, they developed a way to stabilize the beating heart so they could obtain high-quality images of immune cell trafficking.

The same team also has used the technique to image immune cells in mouse lungs, which also move as the mice breathe but not to the same extent as the heart. And other scientists have used two-photon imaging to watch neutrophils travel into the skin, liver and other organs. Surprisingly, the researchers are finding that the trafficking of neutrophils differs from one organ to the next.

"Each organ seems to have its own requirements for signaling and attracting inflammatory cells," says Kreisel, who also is an associate professor of surgery. "It is as if each organ has its own zip code. Now, we have the ability to identify all the cells and signaling molecules that play a part in heart inflammation and can block particular pathways to see if we can prevent organ damage."

Li W, Nava RG, Bribriesco AC, Zinselmeyer BH, Spahn JH, Gelman AE, Krupnick AS, Miller MJ, Kreisel D. Intravital 2-photon imaging of leukocyte trafficking in beating heart. Journal of Clinical Investigation. July 2012.

The research is supported by the National Heart Lung and Blood Institute (1R01HL094601) and the National Institute of Allergy and Infectious Diseases (AI077600).

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Caroline Arbanas | EurekAlert!
Further information:
http://www.wustl.edu

More articles from Health and Medicine:

nachricht On track to heal leukaemia
18.01.2017 | Universitätsspital Bern

nachricht Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

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...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Explaining how 2-D materials break at the atomic level

18.01.2017 | Materials Sciences

Data analysis optimizes cyber-physical systems in telecommunications and building automation

18.01.2017 | Information Technology

Reducing household waste with less energy

18.01.2017 | Ecology, The Environment and Conservation

VideoLinks
B2B-VideoLinks
More VideoLinks >>>