Macrophages are cells that play a major role in inflammation -- they detect and swallow invading microbes and foreign particles, such as asbestos microfibers. At the same time, activated macrophages release cytokines, small proteins that serve as signals to recruit and activate other immune cells for assistance.
To produce and secrete one major inflammatory cytokine, interleukin-1beta (IL-1beta), macrophages employ molecular machines called inflammasomes. One of the most functionally diverse inflammasomes is the NLRP3-inflammasome, which releases IL-1beta when stimulated by toxins and microparticles such as silica, asbestos or cholesterol microcrystals.
However, foreign particles don't act directly on the NLRP3-inflammasome. Instead, the team found, foreign particles damage the macrophage's mitochondria -- the cell's energy-producing "power plant." In turn, damaged mitochondria release signals that activate the NLRP3-inflammasome and keep it cranking out IL-1beta.
That's a good thing if your body needs to clear out invading particles or microbes, but continuous production of IL-1beta is very dangerous -- it can easily lead to an inflammatory chain reaction that results in multi-organ failure, septic shock and death. The body needs a way to turn off IL-1beta production by NLRP3-inflammasomes.
To do this, the team discovered, macrophages responding to foreign microbes and irritants also bump up production of p62. This protein coats damaged mitochondria that release inflammasome-activating signals and ensures they are eliminated. Once these damaged mitochondria are removed, the NLRP3-inflammasome de-activates and IL-1beta production is turned off.
http://www.cell.com/cell/fulltext/S0092-8674(15)01721-3
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