Exposure to the mold Aspergillus fumigatus may result in allergic bronchopulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis, or invasive aspergillosis (IA), depending on the host's immune status. Neutrophil deficiency is the predominant risk factor for the development of IA, the most life-threatening condition associated with A. fumigatus exposure. Here we demonstrate that in addition to neutrophils, eosinophils are an important contributor to the clearance of A. fumigatus from the lung. Acute A. fumigatus challenge in normal mice induced the recruitment of CD11b+ Siglec F+ Ly-6G(lo) Ly-6C(neg) CCR3+ eosinophils to the lungs, which was accompanied by an increase in lung Epx (eosinophil peroxidase) mRNA levels. Mice deficient in the transcription factor dblGATA1, which exhibit a selective deficiency in eosinophils, demonstrated impaired A. fumigatus clearance and evidence of germinating organisms in the lung. Higher burden correlated with lower mRNA expression of Epx (eosinophil peroxidase) and Prg2 (major basic protein) as well as lower interleukin 1β (IL-1β), IL-6, IL-17A, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and CXCL1 levels. However, examination of lung inflammatory cell populations failed to demonstrate defects in monocyte/macrophage, dendritic cell, or neutrophil recruitment in dblGATA1-deficient mice, suggesting that the absence of eosinophils in dlbGATA1-deficient mice was the sole cause of impaired lung clearance. We show that eosinophils generated from bone marrow have potent killing activity against A. fumigtaus in vitro, which does not require cell contact and can be recapitulated by eosinophil whole-cell lysates. Collectively, our data support a role for eosinophils in the lung response after A. fumigatus exposure.

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Oxygenators are critical components of extracorporeal circuits used frequently in cardiopulmonary bypass and intensive care, but platelet activation and induction of a complex inflammatory response are usually observed with their use. To improve the biocompatibility of oxygenators, we developed a nitric oxide (NO)-releasing, self-assembled peptide amphiphile nanomatrix. The nanomatrix formed a homogenous coating over the microporous hollow fibers as demonstrated by scanning electron microscopy. We quantitated platelet adhesion to the artificial fibers by measuring absorbance/area of platelets (Abs/A; nm/m2) using acid phosphatase assay. There was a 17-fold decrease in platelet adhesion to the nanomatrix (Abs/A = 0.125) compared to collagen controls (Abs/A = 2.07; p<0.05) and a 22-fold decrease compared to uncoated fibers (Abs/A = 2.75; p<0.05). Importantly, the nanomatrix coating did not impede oxygen transfer in water through coated and uncoated fiber modules (p>0.05) in a bench top test circuit at different flow rates as estimated by change in partial pressure of oxygen in relation to water velocity through fibers. These findings demonstrate the feasibility of coating microporous hollow fibers with a NO-releasing, self-assembled amphiphile nanomatrix that may improve the biocompatibility of the hollow fibers without affecting their gas exchange capacity.