Leslie's "Mast cells show their might" 2010

From Biol557

• Everybody hates mast cells because they are at the heart of allergic reactions.
  • Some researchers have even suggested erradicating them.
• But that's a bad idea because mast cells connect the innate and adaptive immune systems and even detoxify snake and bee toxins.
• Recent research, however, shows that mast cells are at the heart of many diseases like MS, rheumatoid arthritis, cancer, and atherosclerosis.
• We found a strain of mice that don't have mast cells and we can use them to learn more about the mast cell.

[edit] The good

• Mast cells generate a diverse set of chemicals and biologically active products.
• Mast cells store all these things in granules and dump the granules when antibodies on their surface bind an antigen.
• This dumping of chemicals causes everything from a runny nose and hives to anaphalactic shock.
• Since they don't seem to pull their weight in the immune system and we get lots of down sides, the question is "why are they there?"
• Two papers in Nature in 1996 showed that mice without mast cells couldn't fight bacterial infections as well as those that could.
  • This changed the way we think about mast cells because they were the first to show that mast cells could be as critical as life or death.
• Mast cells are the quintessential first responder in the immune system: they are everywhere a pathogen might want to get in.
• Mast cells can phagocytize but their MO is to dump their granules, filled with stuff like TNF which promotes inflammation and attracts neutrophils.
• We used to think that mast cells just showed up and popped, but now we're seeing evidence that they dole out cytokines in a controlled, specific way to control other immune cells.
• Mast cells can enlist the adaptive immune cells, too--B and T cells.
• Remember, however, that a T cell cannot be activated straight away by a mast cell, so mast cells help promote the needed interaction between T cells and antigen presenting cells.
• Thus, mast cells release factors like TNF which spurs dendritic cells to move toward the lymph nodes where T cells are waiting to be activated.
• There is now evidence that mast cells are involved in the regulation of self-immune response, too. It seems that mast cells are the enforcers of the T cell commands of when an immune response should and shouldn't be set off. It is surprising that an innate immune cell like the mast cell is so intimately involved.

[edit] The bad

• It seems that mast cells may be a factor causing rheumatoid arthritis because mice without mast cells don't develop the condition and mast cells have been shown to release IL1 which attracts inflammation-inducing cells to the joints.
• It has been shown that MS symptoms set in later in mice that don't have mast cells (and not just a lack of CNS mast cells).
• It seems that mast cells (which have been shown to inhabit plaque in the arteries) may help to loosen it up, thus causing heart attacks.
  • Indeed, in mice strains that are prone to atherosclerosis, when mast cells are removed, the plaques are smaller and less likely to fracture. Researchers think this has to do with mast cells' ability to stimulate local cells to release cathepsins which cause problems.
• Even more, mice with mast cells were more likely to go into ventricular tachycardia (a deadly fibrillation that often occurs once blood flow is returned to the heart) than mice that had to mast cells.

[edit] The ugly

• It seems that cancers may take advantage of the otherwise-benevolent pro-angiogenesis mood of mast cells, thus garnering nutrients for rampant growth.
• In Hodgkins lymphoma, when tumor cells nuzzle up with mast cells the mast cells release inflammatory signals that, instead of ending in distruction of the cancer, abet in garnering tumor growth.
• Scientists are still trying to figure out how mast cells can pull in both directions on so many issues, like increasing and decreasing inflammation, etc.
• It seems that mast cells specialize their reactions for the tissue in which they have grown up in. Thus there are a multitude of varieties of mast cells.
• One caveat of all this research is that it is all done in mice and we don't have a human model to move on to.
• Researchers are trying to convert drugs that work on allergic reactions and asthma to work on atherosclerosis and many of the other conditions previously discussed.
• There is still lots to be learned about mast cells.
• At least one researcher says he wouldn't have his mast cells removed even if he could.