Analyzing the Biological Entity of Nanomaterials - Safety of Nanomaterials along Their Lifecycle - page 77

deposit in this upper part of the lungs are efficiently trapped in this mucus layer, and
are constantly transported in the cranial direction, where they can be swallowed
and subsequently processed in the GIT (see Section 4.1). This so-called mucociliary
clearance is a very efficient protective mechanism to remove particulate matter from
the lungs. Thus, understanding the interactions between nanomaterial and mucus
of the upper airways is only of minor relevance. Apart from the conducting airways,
the lung lining fluid is mostly a very thin liquid film (0.09-0.89 μm) that spreads
over the whole respiratory tract from the peripheral to the central lungs (Bastacky
et al. 1995). Its major integral component is pulmonary surfactant (PS), a surface-
active film located at the air-liquid interface. PS is a complex mixture of about 90%
lipids and about 10% proteins. Phospholipids (PL) account for about 80% of the lipid
fraction and the majority are phosphatidyl-choline (PC), -gylcerol (PG), and -inosi-
tol (PI) species (with PC accounting for the biggest PL population). The remaining
5%-10% of the lipid fraction are cholesterol, sphingolipids, glycerides, and fatty
acids (Blanco and Pérez-Gil 2007). Among the protein species, which account for
5%-10% by weight, four specific surfactant proteins (SP) are known: SP-A, -B, -C,
and -D (Goerke 1998).
PS fulfills two principal functions: a biophysical and an immunological function.
The biophysical function—which is governed by the phospholipid fraction—is to
lower the surface tension at the air-liquid interface and thereby prevent the alveoli
from collapsing during exhalation (Rugonyi et al. 2008). The immunological role of
PS in the host defense system of the lungs is mainly attributed to surfactant proteins,
namely SP-A and -D, both belonging to the collectin protein family (Kishore et al.
2006). Their localization at the air-liquid interface makes them ideally situated to
bind foreign materials (e.g., inhaled nanomaterials) to facilitate uptake by immuno-
competent cells (e.g., alveolar macrophages), or to trigger and/or control inflamma-
tory processes (Wright 2005).
Inhaled nanomaterial will be efficiently displaced into the subphase of the lung
lining fluid (Schürch et al. 1990), where they can get in contact with PS components
(e.g., surfactant PLs or SPs) or other constituents of the lung lining fluid (immu-
noglobulins, albumin, or other proteins). The bio-nano interactions occurring here
might be very decisive regarding the further biological fate of the nanomaterial. It
is therefore important to consider these specific components of the lung lining fluid
with respect to in situ characterization of nanomaterials, and to study their binding
to nanomaterials, as well as subsequent biological effects.
4.3.2 a vailaBle m odels for l ung l lining f luid
Unfortunately, there are no standardized models available for the lung lining fluid
as test medium to study bio-nano interactions in the lungs—in contrast to, for
instance, models for the systemic circulation where plasma or serum samples of
standardized quality can be accessed in large quantities. The lung lining fluid is
a thin liquid layer present at the air interface of the lungs, and is only accessible
via broncho-alveolar lavage (BAL). This implies that access to human material is
very limited, as BAL can only be performed during bronchoscopy of patients—
whose lungs are often pathophysiologically altered. For this reason, animal sources