Satratoxin‐G from black mold induces rhinitis and apoptosis of olfactory sensory neurons in the nasal airways of rhesus monkeys

Abstract

Satratoxin‐G (SG) is a macrocyclic trichothecene mycotoxin of Stachybotrys chartarum, a black mold suggested to contribute to adverse health effects associated with water‐damaged buildings. We recently reported that intranasal exposure to SG evokes apoptosis of olfactory sensory neurons (OSNs) and acute inflammation in the nose and brain of mice. To assess the potential human risk of nasal airway injury and neurotoxicity, we developed an in vivo model of SG exposure in monkeys, whose nasal airways more closely resemble those of humans. Male, 2–3 year‐old rhesus macaques received either a single intranasal instillation of 20μg SG (high‐dose, n=3), or daily instillation of 5μg SG for four days (repeated low‐dose, n=3) in one nasal passage. Saline vehicle alone was administered to the contralateral nasal passage. Animals were euthanized 24h post‐exposure. Nasal tissues were examined for SG‐induced injury in the olfactory epithelium (OE). In both groups, SG induced acute rhinitis in the OE, resulting in a 9‐fold increase in intraepithelial neutrophils versus controls. SG also induced olfactory epithelial atrophy and apoptosis of OSNs in both groups. OSN apoptosis was identified with immunohistochemistry for caspase‐3 and electron microscopy for ultrastructural changes. High‐dose and repeated low‐dose SG elicited a 13% and 66% reduction in OSN volume density, and a 14‐fold and 28‐fold increase in apoptotic cells of the OE, respectively. Caspase‐3 immunoreactivity was detected in the OE and the olfactory nerve bundles in the underlying nasal mucosa in both SG groups. This model provides new insight into the potential human risk of nasal airway injury and neurotoxicity caused by exposure to S. chartarum in water‐damaged buildings.Funded by: NIH P51 RR000169