New study confirms immune cells are guided by gradients
The outlines of cells constituting the lymphatic vessel are marked in green and the chemokine CCL21 which is deposited in these vessels is blue. Red color demarcates all vessels - lymphatic and blood vessels. Credit: Michele Weber and Michael Sixt
(Medical Xpress)—A group of researchers in Austria and Switzerland has for the first time proven that immune cells migrate along chemical concentration gradients. This process has long been assumed but never demonstrated experimentally in living tissues.
Immune cells are known to leave the blood stream and migrate through tissues in search of bacteria, viruses, and other invaders, and then enter lymphatic vessels and return to the circulation system. Now the new research confirms exactly how they move through the tissues and find their way out again.
It was thought that immune cells are guided through tissues along gradients of chemokines, which are a class of proteins secreted by cells and known to guide the movement of cells during embryonic development. Cancer cells are also thought to follow the same gradients to disseminate in the body. This process had been assumed and demonstrated in cell cultures but had never before proven in vivo.
The researchers, led by Assistant Professor Michael Sixt of the Institute of Science and Technology Austria, studied interstitial dendritic cells (a type of leukocyte or white blood cell) in the skin of mice and a chemokine called CCL21. Through quantitative imaging, they were able to watch the cells navigating through the tissues.
Chemokines were formerly known as cytokines, and there are several different families of these proteins. The C-C chemokines are so called because they have two adjacent cysteines. In humans, CCL21, or Chemokine (C-C motif) ligand 21, is expressed by a gene on chromosome 9.
This video is not supported by your browser at this time.
Time-lapse movie of dendritic cells (red) entering lymphatic vessels (green), in a mouse ear explants. Credit: Michele Weber and Michael SixtThe scientists showed that CCL21 is produced by the endothelial cells in the lymphatic vessel and the chemokine then spreads out into the tissues to form a steeply decaying concentration gradient. They were able to map out the gradients and compare these with the migration routes actually taken by the immune cells, and proved that from a distance of about 90 micrometers the cells followed the concentration gradient and located the lymphatic vessel by moving towards the greater concentration of CCL21.
The researchers were also able to demonstrate that the concentration gradients were bound to the tissues (immobilized) and not soluble. They did this by swamping the gradients by adding extra chemokine and by delocalizing the chemokine, which is immobilized to heparan sulfates. The process of migration following immobilized concentration gradients is known as haptotaxis.
Their paper was published in the journal Science.
More information: Interstitial Dendritic Cell Guidance by Haptotactic Chemokine Gradients, Science, 18 January 2013: Vol. 339 no. 6117 pp. 328-332
Directional guidance of cells via gradients of chemokines is considered crucial for embryonic development, cancer dissemination, and immune responses. Nevertheless, the concept still lacks direct experimental confirmation in vivo. Here, we identify endogenous gradients of the chemokine CCL21 within mouse skin and show that they guide dendritic cells toward lymphatic vessels. Quantitative imaging reveals depots of CCL21 within lymphatic endothelial cells and steeply decaying gradients within the perilymphatic interstitium. These gradients match the migratory patterns of the dendritic cells, which directionally approach vessels from a distance of up to 90-micrometers. Interstitial CCL21 is immobilized to heparan sulfates, and its experimental delocalization or swamping the endogenous gradients abolishes directed migration. These findings functionally establish the concept of haptotaxis, directed migration along immobilized gradients, in tissues.
Journal reference: Science
© 2013 Medical Xpress
- Study shows how immune cells navigate through the skin by sensing graded patterns of immobilized directional cues Jan 17, 2013 | not rated yet | 0
- New origin found for a critical immune response Mar 01, 2009 | not rated yet | 0
- Migration alert -- How tumor cells home in on the lymphatic system Jun 11, 2007 | not rated yet | 0
- Hide and seek signals Dec 15, 2011 | not rated yet | 0
- How tumor cells create their own pathways Jul 10, 2012 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
5 hours ago Alright, so in Pathfinder (like Dungeons and Dragons) there's a spell that allows you to lift/move stuff within 25 ft with 5 pounds of force. A...
8 hours ago So energy can only be converted... So when you squeeze the bulb on a blood pressure cuff, you are applying kinetic energy. Then the cuff fills with...
How does momentum, inertia and drag affect the motion of an object?
10 hours ago How does momentum and inertia affect changes in speed, when considering acceleration from thrust, or from decelleration from drag? Say, for a...
What is Time-Varying Voltage?
11 hours ago In circuits, we have no problem saying that the voltage difference between two point is [itex]\cos(\omega t)[/itex], but what does that actually...
Contextual Relationships Between Momentum, Energy, and Force.
13 hours ago *I apologize in advance for the length of this post, if you wish to reduce reading skip to paragraph 5. Or if you are super lazy, the final...
Barometric pressure and the math behind it. Very interesting, I think.
14 hours ago Hey guys, I was actually researching the life of Edmond Halley and discovered that he discovered the relationship between barometric pressure and the...
- More from Physics Forums - Classical Physics
More news stories
Raising hopes for cell-based therapies, UC San Francisco researchers have created the first functioning human thymus tissue from embryonic stem cells in the laboratory. The researchers showed that, in mice, ...
Immunology May 16, 2013 | 4.8 / 5 (5) | 0 |
Researchers from CNRS, Université Toulouse III - Paul Sabatier and IRD have elucidated new molecular mechanisms involved in resistance to visceral leishmaniasis, a serious parasitic infection. They have shown that dectin-1 ...
Immunology May 16, 2013 | not rated yet | 0
Women's immune systems age more slowly than men's, suggests research in BioMed Central's open access journal Immunity & Ageing. The slower decline in a woman's immune system may contribute to women living longer than men. ...
Immunology May 14, 2013 | not rated yet | 0
Newly described type of immune cell and T cells share similar path to maturity, according to new study
(Medical Xpress)—Labs around the world, and a core group at Penn, have been studying recently described populations of immune cells called innate lymphoid cells (ILCs). Some researchers liken them to foot soldiers that ...
Immunology May 14, 2013 | 5 / 5 (3) | 0 |
(Medical Xpress)—Cytokines are molecules produced by immune cells that induce the migration of other cells to sites of infection or injury, promote the production of anti-microbial agents, and signal the production of inflammatory ...
Immunology May 13, 2013 | 5 / 5 (1) | 0 |
Big names in medicine are set to give an upbeat assessment of the war on AIDS on Tuesday, 30 years after French researchers identified the virus that causes the disease.
6 hours ago | 5 / 5 (1) | 0
For combat veterans suffering from post-traumatic stress disorder, 'fear circuitry' in the brain never rests
Chronic trauma can inflict lasting damage to brain regions associated with fear and anxiety. Previous imaging studies of people with post-traumatic stress disorder, or PTSD, have shown that these brain regions can over-or ...
7 hours ago | not rated yet | 0 |
(Medical Xpress)—What if the quality of your work depends more on your focus on the piano keys or canvas or laptop than your musical or painting or computing skills? If target users can be convinced, they ...
19 hours ago | 3.7 / 5 (3) | 0 |
The neural machinery underlying our olfactory sense continues to be an enigma for neuroscience. A recent review in Neuron seeks to expand traditional ideas about how neurons in the olfactory bulb might encode information about ...
18 hours ago | not rated yet | 0 |
In 2008 researchers from the University of Southern Denmark showed that the drug thioridazine, which has previously been used to treat schizophrenia, is also a powerful weapon against antibiotic-resistant bacteria such as ...
16 hours ago | 3.7 / 5 (3) | 0 |