Tuesday, 26 July 2011
Research to Prevent Mucus Overproduction in Airways in Aspergillosis - a new clue
Excessive mucin production is a major debilitating feature of allergic bronchopulmonary mycoses such as ABPA. The mucin characteristically causes major blockages of bronchial airways and is very difficult to remove and is tends to be very sticky and clinging in nature. Mucin production is an important part of the mechanisms that protect our airways as it can bind to harmful microorganisms and prevent them growing, but in some circumstances there appears to be too much mucin produced and it can start to cause problems - not the least of which is suppression of the fine hairs lining our airways (cilia) that brush debris and micro-organisms out of our lungs.
In conditions such as ABPA mucin overproduction also make it difficult to detect and sample the strain(s) of Aspergillus that are infecting, as it can make it very difficult to isolate samples of the fungus and grow it on in laboratory culture plates. It may well also inhibit antifungal drugs from getting at the fungus - for fungal infections mucin is not at all helpful!
If we could control mucin production we should be able to prevent it being overproduced and thus be able to overcome many of the problems faced by both the patients and the team trying to treat them.This recent paper shows that at least in the laboratory mucin production by cells that line the walls of our airways can be selectively stimulated by the presence of Aspergillus fumigatus extracts via the gene MUC5AC.
The suggestion is that one of the ways A. fumigatus can establish itself in our lungs is by overstimulating mucin production, hindering our natural defence mechanisms and allowing the fungus to persist. Importantly the authors show that the induction of mucin can be diminished by administering substances that block the activities of TGF-alpha or epidermal growth factor (EGF), both well characterised gene regulating factors.
It looks like TGF and EGF induction by (as yet unknown) factors in Aspergillus fumigatus might be causing a cascade of induction of mucin causing overproduction via other known intermediaries, the result of which we apparently see happening in human patients. We may now have several new potential targets to use to improve treatment of ABPA and similar diseases
NOTE: we mentioned genome sequencing in earlier blogs, but an equally important relatively new technology that has followed from the ability to sequence an entire genome is that of microarrays where we can quickly determine the expression of all of the genes in an organism under specific circumstances. This paper being discussed in this blog is an example of a discovery made using this technology.