Brevetoxin-2 induces an inflammatory response in an alveolar macrophage cell line

Brevetoxins, the algal toxins produced by Karenia brevis during red tide blooms, adversely impact health following ingestion or inhalation. Inhalation of brevetoxins results in a variety of acute symptoms including coughing, wheezing, and shortness of breath. Analysis of manatee lungs following death by purported brevetoxicosis has identified brevetoxin accumulation within macrophages, with pathological manifestions of lung congestion, inflammation, and edema. The goals of this work were to specifically examine effects of brevetoxin-2 on alveolar macrophages, a key cell in responding to toxins in the lung, as well as to determine if brevetoxin-2 results in an inflammatory response and/or direct cytotoxicity. Exposure of an alveolar macrophage cell line (MH-S) to an environmentally and physiologically relevant dose of brevetoxin-2 (0.5 μg/ml) did not significantly alter cellular growth over a 24 h time period. However, exposure of MH-S cells to brevetoxin-2 for 6 h increased phagocytosis of latex beads, increased secretion of interleukin (IL)-2, IL-4, and tumor necrosis factor-α, and decreased secretion of IL-5. Very few changes were seen in gene expression following 3 or 6 h exposure to brevetoxin-2. These results show that brevetoxin-2 induced an immune response indicative of inflammation in an alveolar macrophage cell line, indicating that inhalation of brevetoxin-2 may lead to lung inflammation through an alveolar macrophage-initiated pathway.