Interactions of nanoparticles with pulmonary structures and cellular responses

Abstract

Combustion-derived and synthetic nano-sized particles (NSP) have gained considerable interest among pulmonary researchers and clinicians for two main reasons. 1) Inhalation exposure to combustion-derived NSP was associated with increased pulmonary and cardiovascular morbidity and mortality as suggested by epidemiological studies. Experimental evidence has provided a mechanistic picture of the adverse health effects associated with inhalation of combustion-derived and synthetic NSP. 2) The toxicological potential of NSP contrasts with the potential application of synthetic NSP in technological as well as medicinal settings, with the latter including the use of NSP as diagnostics or therapeutics. To shed light on this paradox, this article aims to highlight recent findings about the interaction of inhaled NSP with the structures of the respiratory tract including surfactant, alveolar macrophages, and epithelial cells. Cellular responses to NSP exposure include the generation of reactive oxygen species and the induction of an inflammatory response. Furthermore, this review places special emphasis on methodological differences between experimental studies and the caveats associated with the dose metrics and points out ways to overcome inherent methodological problems.

Unveiling the Molecular Structure of Pulmonary Surfactant Corona on Nanoparticles

“…Indeed among all potential portals of entering the human body, the respiratory system is the most susceptible to particle invasion due to its large surface area in direct contact with the environment. 14 With their small size, a large portion of inhaled NPs can penetrate the respiratory tracts and deposit in the deep lung, where the NPs first interact with the pulmonary surfactant (PS) lining layer of alveoli and develop the so-called PS biomolecular corona. 15−17 The PS is composed of approximately 90% lipids, including various phospholipids and cholesterol, and 10% proteins (named SP-A, SP-B, SP-C, and SP-D) by weight.…”

Particulate matter phagocytosis induces tissue factor in differentiating macrophages

“…PM triggers pulmonary oxidative stress and inflammation by heterogeneous and complex mechanisms, with several responses according to different properties of PM particles. Indeed the ultrafine particles may directly enter cells via nonphagocytic pathways and then impair intracellular organelles like mitochondria (Mühlfeld C et al 2008); Ultrafine particulate has also been demonstrated to promote vascular calcification by activating NFKB signaling (Li R et al, 2013).…”

Impact of Particulate Matter Exposition on the Risk of Ischemic Stroke: Epidemiologic Evidence and Putative Mechanisms

“…In addition, up to 80% of PM, predominantly the coarse fraction, is able to enter pulmonary parenchyma by transcytosis through macrophages and alveolar epithelium cells. 44 These particles can access the pulmonary circulatory system and are subsequently adducted by plasma proteins. 44 As a consequence, the occurrence of these PM-protein complexes in pulmonary and systemic circulations can induce systemic immune responses, particularly in adipose tissue.…”

“…44 These particles can access the pulmonary circulatory system and are subsequently adducted by plasma proteins. 44 As a consequence, the occurrence of these PM-protein complexes in pulmonary and systemic circulations can induce systemic immune responses, particularly in adipose tissue. 43,44 In summary, PM exposure is capable of triggering a complex immune response, which is initiated locally in the lung parenchyma and which subsequently activates systemic proinflammatory cascades (Figure 1).…”

“…44 As a consequence, the occurrence of these PM-protein complexes in pulmonary and systemic circulations can induce systemic immune responses, particularly in adipose tissue. 43,44 In summary, PM exposure is capable of triggering a complex immune response, which is initiated locally in the lung parenchyma and which subsequently activates systemic proinflammatory cascades (Figure 1). Both mechanisms, the proinflammatory reaction of the lungs and the translocation of particles to other organs, are thought to be responsible for the endothelial dysfunction after PM exposure.…”