n-acetylcysteine as an antifungal agent?

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1: J Allergy Clin Immunol. 1990 Nov;86(5):726-31.Links

Allergens as proteases: an Aspergillus fumigatus proteinase directly

induces human epithelial cell detachment.

BW, Venaille TJ, Mendis AH, McAleer R.

Department of Medicine, University of Western Australia, Nedlands.

Allergic bronchopulmonary aspergillosis (ABPA) is characterized by

pulmonary and systemic allergic and inflammatory processes triggered by

fungal antigens. Airway damage is a feature of this disorder, and

although Aspergillus-derived proteinases have been described, the

capacity of Aspergillus, however, to directly induce damage to human

epithelium has not previously been studied. We therefore cultured

Aspergillus fumigatus from two patients with ABPA, extracted mycelial

products by sonication and filtration, and then evaluated their

capacity to induce epithelial cell (EC) desquamation from basement

membrane using an in vitro model that uses intact human amniotic EC and

native basement membrane. A. fumigatus extracts induced detachment of

EC in a dose-dependent fashion, producing up to 34% +/- 6% detachment

(p less than 0.05 compared to medium alone). Enzyme analysis of A.

Fumigatus extract using synthetic substrates revealed the presence of a

number of different enzymes; therefore, studies with specific

proteinase inhibitors were undertaken to identify the proteinase(s)

responsible for detachment.

---here is the part that I think is important---

A. Fumigatus-induced desquamation was

partially inhibited by phenylmethylsulfonylfluoride and substantially

inhibited by glutathione and N-acetylcysteine,

---

.... but not by alpha

1-antitrypsin, 1,10 phenanthroline, ethylenediaminetetraacetic acid,

aprotinin, or soybean trypsin inhibitor at concentrations that inhibit

other serine- or metalloproteinases. Gel filtration of the extract with

a Sepharose 6B column revealed that the major epithelium-detaching

activity appeared in the 20 to 35 kd fraction. Comparison with

proteinase standards suggested a role for a chymotrypsin-like

proteinase. Thus, A. fumigatus releases a proteinase that is directly

able to induce EC detachment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID: 2229838 [PubMed - indexed for MEDLINE]