Particles Interact with Key Components of Lung Lining Fluid

Michaela Kendall (1), Ping Ding (1), Kevin Kendall (1), Howard Clark (2)

(1) Chemical Engineering, Birmingham University, Birmingham, UK, B15 2TT (2) School of Medicine, Southampton University, Southampton, UK,

     Abstract Number: 233
     Last modified: November 9, 2009

Abstract
Particulate matter (PM) with small aerodynamic diameters – including nanoparticles (NPs), and PM of specific length to diameter ratios or low density – access the lower lung in greater quantities than PM with larger aerodynamic diameters. Initially PM impacts on the surfactant lung lining layer. This layer enables oxygen exchange, lung expansion and also provides primary host defence against depositing foreign material, such as solid and biological particles. Following lung deposition, there is evidence that particles may translocate from the lung to the circulatory system and other organs.

We hypothesized that the initial opsonisation of depositing PM by lung lining polymers in the lower lung alters the downstream behaviour of invading particles. We therefore measured the effects of this polymer attachment on particle behaviour and in cellular responses to particles. We developed a collaboration between scientists in the physical and biological sciences based in Chemical Engineering of University of Birmingham (UK), where state-of-the-art particle characterisation techniques such as dynamic light scattering (DLS) and Nanosight were available. Lung surfactant polymer materials were bought commercially or supplied by Southampton University Medical School (UK). Experimental methods developed by Uludag University (Turkey) were built-upon. The aims of the study were to:

1. Test a novel hypothesis on PM and NP damage mechanisms using cross-disciplinary state-of-the-art analytical techniques from environmental science, nanotechnology and molecular biology; i.e. that polymers are sequestered to particle surfaces, such that the polymer protective functions are lost.
2. Offer hypotheses of short term health effects of airborne PM/nanoparticle exposures using this PM mediated damage hypothesis.

Interactions between a range of particles and NPs (homogeneous polystyrene and silica) and human lung surfactant polymers were investigated. The methodology was to take several particle types, mix them with lung surfactant components such as DPPC, collectins such as SP-A and SP-D and fibrinogen, then to observe the effects caused by sequestering of the polymer molecules on the PM surfaces. Changes in size distribution, zeta potential and morphology were characterised. It was found that particles tended to aggregate in these polymers in a size dependent way and zeta potential changes were observed. Particle aggregation was observed with ESEM and indicated that the aggregation mechanism was different for different polymers. The morphology of particle surfaces was observed to influence aggregation rate, by determining the biologically available surface area. At very low polymer concentrations, the interaction of collectins (surfactant proteins rSP-D, SP-D and SP-A) with NPs were calcium dependent, consistent with the literature. We demonstrate that the lung lining polymers were adsorbed onto the PM surfaces, that the zeta potential was altered, that particle aggregation was promoted and that microscopy confirms polymer deposition and rapid aggregate formation. Such interactions will have significant consequence for particle clearance in the lung leading to polymer disruption and expulsion from the system. The authors kindly acknowledge the support of the UK Natural Environment Research Council (NERC).