Aerosolized Harmful Algal Bloom Toxin Microcystin-LR Induces Type 1/Type 17 Inflammation of Murine Airways

Toxins (Basel). 2024 Nov 1;16(11):470. doi: 10.3390/toxins16110470.

Abstract

Harmful algal blooms are increasing globally and pose serious health concerns releasing cyanotoxins. Microcystin-LR (MC-LR), one of the most frequently produced cyanotoxins, has recently been detected in aerosols generated by the normal motions of affected bodies of water. MC-LR aerosol exposure has been linked to a pro-inflammatory influence on the airways of mice; however, little is understood about the underlying mechanism or the potential consequences. This study aimed to investigate the pro-inflammatory effects of aerosolized MC-LR on murine airways. C57BL/6 and BALB/c mice were exposed to MC-LR aerosols, as these strains are predisposed to type 1/type 17 and type 2 immune responses, respectively. Exposure to MC-LR induced granulocytic inflammation in C57BL/6 but not BALB/c mice, as observed by increased expression of cytokines MIP-1α, CXCL1, CCL2, and GM-CSF compared with their respective vehicle controls. Furthermore, the upregulation of interleukins IL-17A and IL-12 is consistent with Th1- and Th17-driven type 1/type 17 inflammation. Histological analysis confirmed inflammation in the C57BL/6 lungs, with elevated neutrophils and macrophages in the bronchoalveolar lavage fluid and increased pro-inflammatory and pro-resolving oxidized lipids. In contrast, BALB/c mice showed no significant airway inflammation. These results highlight the ability of aerosolized MC-LR to trigger harmful airway inflammation, requiring further research, particularly into populations with predispositions to type 1/type 17 inflammation.

Keywords: MC-LR; aerosol; harmful algal bloom; inflammation; microcystin.

MeSH terms

  • Aerosols
  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Cytokines / metabolism
  • Female
  • Harmful Algal Bloom*
  • Inflammation / chemically induced
  • Lung / drug effects
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Marine Toxins* / toxicity
  • Mice
  • Mice, Inbred BALB C*
  • Mice, Inbred C57BL*
  • Microcystins* / toxicity
  • Th17 Cells / drug effects
  • Th17 Cells / immunology

Substances

  • Microcystins
  • Marine Toxins
  • cyanoginosin LR
  • Aerosols
  • Cytokines