Complement component 5a

At least, again, murine model, highly transgenic animals, but still you get that kind of information.

More about complement, the C3B, C5A, and the all-important ubiquitous C1Q.

they can actually prevent netosis from DNA activity.

So again, you can't always see these systems as being either promotive or preventative.

in association with interleukin-1-beta, tumor necrosis factor-1-alpha, and interleukin-8, or sometimes 6.

This will link back up to binding to and activating chemokine receptors.

including those chemokine receptors, which are hosting as ligand the complement proteins, which are proteases, remember, C3A and C5A.

Those then become the chemokine receptors known as C3AR, C5AR1, all of which further activate those enzymes, such as NOX, involved in NET production.

Absolutely, yeah.

We are actually specialized in the terminal part of the complement system, the C5A as the key activation product of the complement system and its receptor C5AR.

It goes back to work at the University of Michigan.

The other founder, Renfeng Guo, and myself, we were both postdocs in a well-known complement lab, Peter Ward, and we studied really this pathway.

Yeah, some people call it AAV for short, right? Right,

AAV for short, antisocial vasculitis.

So the interesting part, ANCA means antineutrophil cytoplasmic antibodies.

So you make autoantibodies in your system that are directed against certain structures inside the cell that has the highest density of C5A receptors, which is the neutrophil.

So what are the key A fragments?

We have C3A, C4A, and C5A, which are known as anaphylatoxins.

They circulate and trigger massive mass cell degranulation, releasing histamine and causing profound vasodilation and vascular permeability.

They really ramp up the inflammation.

We also have C3A and C5A acting as incredibly potent chemoattractants, pulling in huge waves of additional neutrophils and macrophages to the site.

Then we have C3B.

Ah, C3B.