Biomedical Engineering Reference
In-Depth Information
20.7.4 g
raNuloMa
f
orMatIoN
The granuloma is a small nodule or a small collection of immune cells produced when the immune
system attempts to remove foreign substances, but cannot eliminate them. CNTs and asbestos both
were found to cause granulomas in mice exposed for 7 days. Intratracheal instillation of SWCNTs
(diameter ranging from 0.7 to 1.5 nm) in the lungs of rats lead to the obstruction of the airway as a
result of granuloma formation with a 15% mortality within a day [17].
20.7.5 a
poptosIs
Apoptosis is the process of programmed cell death that may occur in multicellular organisms.
SWCNTs caused apoptosis of five carbon-based nanomaterials, including SWCNTs and MWCNTs
for toxicity in human fibroblast cells. Some researchers hypothesized that when dispersed with
small surface hydrophobic materials, CNTs show increased toxicity and also proposed that the
mechanism of toxicity due to the CNT was due to the extracellular matrix protein signaling result-
ing in changes in the cell skeleton and the subsequent displacement of organelles, resulting in mem-
brane deformation and finally, apoptosis [11].
20.8 CARBON NANOPARTICLE-INDUCED OXIDATIVE STRESS
The oxidative stress results in cells exposed to CNPs. According to the hierarchical oxidative
stress hypothesis, the lowest level of oxidative stress is associated with the induction of antioxidant
and detoxification enzymes. The genes that encode the phase II enzymes are under the control of
the transcription factor Nrf-2. Nrf-2 activates the promoters of phase II genes via an antioxidant
response element. Defects or aberrancy of this protective response pathway may determine disease
susceptibility during ambient particle exposure. At higher levels of oxidative stress, this protec-
tive response is overtaken by inflammation and cytotoxicity. Inflammation is initiated through the
activation of proinflammatory signaling cascades (e.g., mitogen-activated protein kinase and NF-jB
cascades), whereas programmed cell death could result from mitochondrial perturbation and the
release of proapoptotic factors [18].
Exposure to NPs is a source of increasing ROS, leading to oxidative stress. Three factors mostly
govern the process of ROS generation by NPs as outlined by Knaapen et al.: (i) active redox cycling
on the surface of NPs, particularly, the metal-based NPs; (ii) oxidative groups functionalized on
NPs; and (iii) particle-cell interactions, especially in the lungs where there is a rich pool of ROS
producers such as the inflammatory phagocytes, neutrophils, and macrophages [18]. Owing to the
overproduction of ROS, a series of cytokine cascades are activated, which include an upregula-
tion of interleukins (IL), kinases, and tumor necrosis factor α (TNF-α) proinflammatory signaling
processes as a counterreaction to oxidative stress. It has been observed in some studies on C60
fullerenes that these NPs induce elevation of proinflammatory enzymes, such as IL-1, TNF-α,
IL-6, macrophage inhibitory protein, and monocyte chemotactic protein in rodent lungs. When
receptor tyrosine kinases, mitogen-activated protein kinases, and transcriptional factors, such as
nuclear factor-κB and signal transducer and activator of transcription 1, are activated, the genes
involved in inflammation and fibrosis are transcribed and expressed. Stimulation of IL-1b and
TNF-α complicates the expression of profibrotic proteins. More specifically, the latter is known to
increase the production of the transforming growth factor (TGF)-b1, which potentiates collagen
deposition by fibroblasts, while the former is associated with the expression of a platelet-derived
growth factor (PDGF)-AA and its receptor, PDGF receptor-a, which increases proliferation of
myofibroblasts, promoting the formation of immature collagenous tissue within the lung. Hence,
oxidative stress in a cell is usually measured as a function of ROS assay due to the production of
free radical species [18].
