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Lack of vessel wall elastolysis in human invasive pulmonary aspergillosis
D W Denning1, P N Ward, L E Fenelon
1Regional Department of Infectious Diseases and Tropical Medicine, Monsall Hospital, Manchester, United Kingdom.
Abstract:
In experimental studies, the apparent ability of Aspergillus fumigatus isolates to produce elastase in agar plates correlates with their ability to cause invasive pulmonary aspergillosis in mice pretreated with cortisone. Thus, elastase production may govern the pathogenicity of particular isolates. If this is so, then disruption of the elastic layers within blood vessel walls in invasive aspergillosis would be expected. To test this hypothesis, tissue blocks were prepared from nine patients with invasive pulmonary aspergillosis. Separate but immediately adjacent histological sections were stained by the Grocott and periodic acid-Schiff methods for fungal hyphae and by the elastic van Gieson technique for elastic tissue. Comparison of those segments of vessel walls infiltrated by hyphae with those not infiltrated by hyphae showed no overall loss of elastic tissue. Material from five of the cases was also stained with an unconventional combination of histochemical stains, allowing accurate identification of both fungal hyphae and elastic laminae in the same histological sections. The results showed no more disruption of elastic laminae than would be expected from simple physical displacement of elastic laminae. We conclude that if elastolysis contributes at all to invasion of vessel walls by aspergilli, then it seems to be very localized and/or transient.
Insights
Aspergillus fumigatus elastase production may link to invasive pulmonary aspergillosis. However, this study found no significant elastolysis in patient blood vessel walls, suggesting localized or transient effects.
Area of Science:
- Medical Mycology
- Pathology
- Histochemistry
Background:
- Experimental studies suggest Aspergillus fumigatus elastase production correlates with invasive pulmonary aspergillosis pathogenicity.
- Elastase activity could explain the disruption of elastic layers in blood vessel walls during invasive aspergillosis.
- Investigating the role of elastolysis in fungal invasion of vascular tissue is crucial for understanding disease mechanisms.
Purpose of the Study:
- To investigate the hypothesis that elastolysis by Aspergillus fumigatus causes disruption of elastic laminae in blood vessel walls in invasive pulmonary aspergillosis.
- To determine the extent of elastic tissue damage in human tissues affected by invasive aspergillosis.
Main Methods:
- Histological examination of tissue blocks from nine patients with invasive pulmonary aspergillosis.
- Staining with Grocott and periodic acid-Schiff methods to identify fungal hyphae.
- Staining with elastic van Gieson technique to visualize elastic tissue.
- Use of a combined histochemical staining method for simultaneous visualization of fungi and elastic laminae.
Main Results:
- No overall significant loss of elastic tissue was observed in the vessel walls infiltrated by fungal hyphae.
- Histochemical analysis revealed no more disruption of elastic laminae than expected from physical displacement by fungal growth.
- Elastolysis, if present, appears to be highly localized or transient in the affected vascular tissue.
Conclusions:
- The study challenges the significant role of elastolysis in the vascular invasion process of Aspergillus fumigatus.
- Findings suggest that physical displacement by fungal hyphae is a more likely explanation for observed changes in vessel walls.
- Further research may be needed to elucidate the precise mechanisms of vascular invasion in invasive pulmonary aspergillosis.