(387c) Inactivation of Lung Surfactant By Phospholipase-Catalyzed Degradation | AIChE

(387c) Inactivation of Lung Surfactant By Phospholipase-Catalyzed Degradation


Squires, T., University of California at Santa Barbara
The alveoli of human lungs are lined by a thin aqueous film with a surfactant layer composed primarily of lipids at the air-film interface. The lung surfactant (LS) layer reduces surface tension and stabilizes the lung against collapse and overdistension, and is thus necessary for respiration. LS is said to be ‘inactivated’, meaning that it loses its ability to moderate surface tension to healthy levels, in pulmonary diseases such as acute respiratory distress syndrome (ARDS) [1]. However, the inactivation mechanism remains unknown. In this investigation we focus on the role of phospholipase (PLA2) in LS inactivation, an enzyme known to be present in increased levels in the lungs of ARDS patients. PLA2 hydrolyzes lipids such as DPPC into palmitic acid (PA) and lyso-PC (LPC) [2,3]. Since PA co-crystallizes with DPPC to form rigid, elastic domains [4], we hypothesize that PLA2-catalyzed degradation establishes a stiff, heterogeneous rheology in the monolayer, which will impair LS function. Here we study the evolution of a DPPC monolayer forming a 2D gel-like network as it is degraded by PLA2. Using interfacial microbutton microrheometry coupled with fluorescence microscopy, we track local rheology and morphology of the actively degrading monolayer. These results are compared to monolayers with fixed amounts of DPPC and its degradation products, simulating the evolving composition of the degrading monolayers.


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[2] Thompson, B. T.; Chambers, R. C.; Liu, K. D. N. Engl. J. Med. 2017, 377, 562-572.

[3] Nakos, G.; Kitsiouli, E. I., Tsangaris, I.; Lekka, M. E. Intensive Care Med. 1998, 24, 296-303.

[4] Ding, J.; Warriner, H. E.; Zasadzinski, J. A. Phys. Rev. Lett. 2002. 88, pp 1-4.