Adverse Health Effects Following Exposure to Aerosolized Cyanotoxins

PROJECT SUMMARY: PROJECT 4 Cyanobacterial harmful algal blooms (cHABs) are on the rise globally and pose serious health concerns due to the release of cyanotoxins, which are harmful to both humans and the environment. Microcystin-leucine arginine (MC-LR) and Microcystin-leucine alanine (MC-LA), two of the most toxic congeners of microcystin produced by cyanobacteria of the genus Microcystis, have recently been shown to have the highest concentration in lake aerosol particles. Adverse health effects following exposure to aerosolized MC-LA remain largely unknown. In the literature and our preliminary data, it has been observed that aerosolized MC-LR exposure of the airways leads to mixed granulocytic inflammation, with abundant indications of a Type 1 neutrophilic response. Granulocytic inflammation drives 4 of the 5 endotypes of asthma, which is the most common airway condition in the world and is associated with an increased risk of cardiovascular disease and stroke. However, the impact that aerosolized MC-LA and MC-LR exposure may have on the over 330 million patients with pre-existing asthma remains unknown. Furthermore, Microcystis constitutes just one subset of a host of toxin-producing species and complex mixtures of toxins in freshwater systems whose health effects are largely unknown. Therefore, the overall hypothesis is that exposure to aerosolized cyanotoxins induces significant inflammation in the airway epithelium and that individuals with asthma are particularly susceptible to cHAB aerosols. To address this hypothesis in Aim 1 we will interrogate the effects of MCs, such as MC-LA, MC-LR, as well as novel freshwater extracts from P1-3 on cell growth, inflammation and metabolism in primary cells and cell lines derived from physiologically distinct regions on the human respiratory tract from asthmatic and non-asthmatic subjects. For Aim 2, an established pre-existing asthma model will be exposed to aerosolized MC-LR and MC-LA (alone and in combination) for evaluation of pulmonary inflammation and toxicity in downstream target organ systems. In Aim 3, a prospective cohort study will be performed in individuals that live, work, and recreate in the Western Lake Erie basin for the assessment of pulmonary function immediately before, during, and after cHAB seasons. Results from this study will provide targeted mechanistic data and will define host absorption, distribution, metabolism, and elimination (ADME) routes of toxins. In addition, with the Community Engagement Core (CEC), we will inform communities around the world of the risks associated with exposure to aerosolized cyanotoxins, and how these environmental toxins may worsen disease in at-risk populations, potentially influencing local, state, and national policies to protect people living on or around affected bodies of water, as well as provide critical information to healthcare professionals.