The role of 12/15-Lipoxygenase in myeloid cells during allergic fungal asthma

---

Presentation Time: 09:45 AM - 10:00 AM
Abstract ID: 5561 - B

Presenting Author:
Mgayya Makullah , Graduate Student Researcher at Tulane Univ. Sch. of Med.

Abstract:

Immunopathogenic mediators derived from the metabolism of arachidonic acid by lipoxygenases are often elevated in severe asthma. Using bone marrow chimeras, we previously reported that 12/15-lipoxygenase (12/15-LOX; Alox15) activity, specifically in hematopoietic cells, negatively contributes to airway hyperreactivity (AHR) during allergic fungal asthma. This warranted investigation into the role of 12/15-LOX in specific hematopoietic cell types during fungal asthma. CD11c is widely expressed on lung dendritic cells and alveolar macrophages. Surprisingly, deletion of 12/15-LOX in these cell types via Cd11c-Cre/Alox15^fl/fl mice revealed no changes in AHR. In contrast, deletion of 12/15-LOX in neutrophils via Mrp8-Cre/Alox15^fl/fl mice resulted in a small but significant reduction in AHR, suggesting that 12/15-LOX expressed by neutrophils drives immunopathogenesis during allergic fungal asthma. We further show that lungs from allergic Mrp8-Cre/Alox15^fl/fl  mice have a reduction in the total number of neutrophils, dendritic cells and gamma delta T cells compared to Mrp8-Cre controls. Changes in cellularity did not correlate with lung cell production of type 1, type 2 or type 17 cytokines, although specific growth factors and chemokines were lower in Mrp8-Cre/Alox15^fl/fl  mice. These results suggest that absence of 12/15-LOX in neutrophils is sufficient for regulating the magnitude of AHR during allergic fungal asthma, which correlated with cellular changes in the lung.