The Role of Neutrophil Extracellular Traps in Human Health
This is a modal window.
The media could not be loaded, either because the server or network failed or because the format is not supported.
Formal Metadata
| Title |
| |
| Alternative Title |
| |
| Author | ||
| License | CC Attribution 3.0 Unported: You are free to use, adapt and copy, distribute and transmit the work or content in adapted or unchanged form for any legal purpose as long as the work is attributed to the author in the manner specified by the author or licensor. | |
| Identifiers | 10.21036/LTPUB10840 (DOI) | |
| Publisher | ||
| Release Date | ||
| Language |
Content Metadata
| Subject Area | ||
| Genre | ||
| Abstract |
|
00:04
Meeting/Interview
00:11
Computer animation
01:02
Meeting/Interview
01:10
Meeting/Interview
01:39
Computer animationDiagram
02:59
Computer animation
03:18
Meeting/Interview
03:37
Computer animationMeeting/Interview
03:54
Computer animation
04:23
Meeting/Interview
04:36
Meeting/Interview
Transcript: English(auto-generated)
00:04
We are trying to understand how the body defends itself against infections. And more specifically, we work on neutrophils. Neutrophils are the most abundant cells in circulation, the first cells to go to a site of infection. And people that don't have function in neutrophils or don't have the right amount
00:22
of neutrophils suffer a lot from infections. Neutrophils have different mechanisms to detect and kill microbes, and we are interested in the production of NETs. And NETs is an acronym that stands for Neutrophil Extracellular Traps that we described a few years ago. So it turns out that when a neutrophil sees a microbe, then it can modify its own chromatin
00:45
and expel it into the milieu or the tissue where the microbes are. And NETs can have different functions. One of them is to kill and prevent the dissemination of the microbe, and another one is to alert the rest of the immune system that there is an infection.
01:02
My interest is to understand now how these NETs are formed and what is their relevance, not only in infectious diseases but also in other diseases. So the neutrophil is a cell that is difficult to work with because there are no cell lines that mimic the activity of the cell.
01:21
That is, most of the experiments we do has to be a cell that came from the circulation either of a patient or a healthy donor or an animal. Now, the purification of these cells is relatively simple, but then comes the challenge of what can we do with them. And we divide our work in several fields. We use a lot of microscopy of different kinds to try to observe how the NETs are made.
01:45
We use biochemistry to try to isolate the components that are required for NET formation. And we use cell biology sometimes to try to reconstruct a cell biological process in vitro to understand how NETs are made.
02:01
Technologically, we can do this in animals, and we do it sometimes in mice. We are setting up a way to do it in fish, which are transparent, and we can observe the neutrophils work in vivo. And many times we collaborate with clinicians so we can obtain samples from patients that have a specific defect in neutrophils, and we can understand the disease and therefore
02:21
understand how NETs are made. When we described the NETs, it was a surprise that neutrophils could die and expose their own chromatin to defend the body against infections. And the challenge then was to try to understand the mechanism of NET formation to validate
02:41
their relevance and also to see in which kind of diseases were the NETs relevant. We are still analyzing the activity of NET formation, how NETs are formed, and this is we know now it has a series of biochemical steps that include the formation of reactive
03:01
oxygen species, the activation of proteases that cut proteins to allow the expansion of the NETs, and a pore-forming protein called gasdermin that allows the explosion of the cell. There are still many questions that we don't understand because this is a unique form, a unique pathway in cell biology. We have also, as many other labs have done, work on the relevance of NETs.
03:22
There is very interesting literature showing that NETs are relevant not only in the defense of infection but also in a series of other diseases like autoimmunity, cancer, and very interesting results also in cardiovascular diseases.
03:40
When we identify the NETs, we realize that it would be an important target to try to control diseases. My lab and many other labs have shown that NETs are important in defending against infections, in which case it would be interesting to make patients have more NETs, but it would be they are deleterious in other forms of infections, of other forms of diseases,
04:04
in which case it would be important to get rid of them. By trying to understand the basic mechanism of how NETs are made, we could identify targets that then my lab or other labs, the scientific community, could try to exploit in order to prevent NET formation and then ameliorate diseases.
04:23
For example, lupus, which is an autoimmune disease where there is very good evidence that NETs are very deleterious. So if we could stop the formation of NETs in lupus, that might be beneficial for patients. So we are biochemists and cell biologists, and we want to understand NET formation
04:44
at the biochemical level. There are still many outstanding questions in the formation of NETs. For example, what is the function of reactive oxygen species? How reactive oxygen species, which are very short-lived, how do they modify other proteins in order to allow the formation of NETs?
05:03
For example, we are also interested in how proteases work. Why do they cleave, why do they break, that allow the expansion of chromatin? Another example would be, once the NETs are made, do they have a specific structure or they are just a mess of different proteins stuck to chromatin?
05:20
And we would like to understand whether this specific distribution of proteins in the NETs are actually relevant in their function.
Recommendations
Series of 34 media