self-recognition mechanism of spleen cells to use CD47 as another component for
surface modification of nanomaterials [31]. CD47 is thought to represent self-signal
for the spleen-resident macrophages.
21.4 Innate Immunity to Nanomaterials
Immune response to the nanomaterials should be understood in the context of how
body is accustomed to respond to invading organisms such as viruses, bacteria,
protozoas and helminths. Most of them are extracellular organisms but can be
engulfed by macrophages or trapped by NET. Platelets also are involved to
cooperate with neutrophils or macrophages and trapped organisms are lysed by
extracellular enzymes released by platelets. Extracellular organisms per se can elicit
immune response, and if this response belongs to adaptive immunity, they elicit
Th2 activation and following stimulation of B cells or Tc cells [32]. Sometimes,
Treg cells previously known to be suppressor T cells are activated and the tolerance
is induced.
21.4.1 How Nanomaterials Meet Bodily Immune System
Investigators do not make hydrophobic nanomaterials to be injected systemically as
they already know very well that hydrophobic materials do aggregate in aqueous
milieu and make no feature of nanomaterials any more. Thus, they hydrophilize first
the surface of the nanomaterials using many known substances. And the most
popular one is polyethylene glycol (PEG) and the recently proposed ones are
polybetaines or other zwitterion polymers [33–35]. PEGylated nanomaterials do not
aggregate and can pass through alveolar capillaries to reach any peripheral tissues
except for brain, testis and cornea, which are sanctuaries having barriers or no
vascularity.
Now investigators would now imagine what will meet injected PEGylated
nanomaterials. PEGylated nanomaterials enter the blood circulation in concentrates
and meet plasma components, mainly proteins consisting of albumins and globulins. Some plasma proteins wrap the nanomaterials with high affinity and are called
hard corona proteins and others bind loosely and transiently and called soft corona
proteins [36–39]. Recent progress of proteomics revealed the heterogeneous constitution of these corona proteins [40]. Corona proteins are believed to influence the
bodily response to the injected nanomaterials and because of this, the response of
the cells cultured in vitro to the nanomaterials mixed in the culture fluid will rarely
simulate the cellular response in vivo [41–43]. In addition, the flow of the nanomaterials along the surface of endothelial cells will affect much the chance of
nanomaterials to encounter the tissue cells. In brief, peripheral endothelial cells see
the circulating nanomaterials very infrequently and might almost ignore the
21 Innate Immunity to Nanomaterials
397
surface modification of nanomaterials [31]. CD47 is thought to represent self-signal
for the spleen-resident macrophages.
21.4 Innate Immunity to Nanomaterials
Immune response to the nanomaterials should be understood in the context of how
body is accustomed to respond to invading organisms such as viruses, bacteria,
protozoas and helminths. Most of them are extracellular organisms but can be
engulfed by macrophages or trapped by NET. Platelets also are involved to
cooperate with neutrophils or macrophages and trapped organisms are lysed by
extracellular enzymes released by platelets. Extracellular organisms per se can elicit
immune response, and if this response belongs to adaptive immunity, they elicit
Th2 activation and following stimulation of B cells or Tc cells [32]. Sometimes,
Treg cells previously known to be suppressor T cells are activated and the tolerance
is induced.
21.4.1 How Nanomaterials Meet Bodily Immune System
Investigators do not make hydrophobic nanomaterials to be injected systemically as
they already know very well that hydrophobic materials do aggregate in aqueous
milieu and make no feature of nanomaterials any more. Thus, they hydrophilize first
the surface of the nanomaterials using many known substances. And the most
popular one is polyethylene glycol (PEG) and the recently proposed ones are
polybetaines or other zwitterion polymers [33–35]. PEGylated nanomaterials do not
aggregate and can pass through alveolar capillaries to reach any peripheral tissues
except for brain, testis and cornea, which are sanctuaries having barriers or no
vascularity.
Now investigators would now imagine what will meet injected PEGylated
nanomaterials. PEGylated nanomaterials enter the blood circulation in concentrates
and meet plasma components, mainly proteins consisting of albumins and globulins. Some plasma proteins wrap the nanomaterials with high affinity and are called
hard corona proteins and others bind loosely and transiently and called soft corona
proteins [36–39]. Recent progress of proteomics revealed the heterogeneous constitution of these corona proteins [40]. Corona proteins are believed to influence the
bodily response to the injected nanomaterials and because of this, the response of
the cells cultured in vitro to the nanomaterials mixed in the culture fluid will rarely
simulate the cellular response in vivo [41–43]. In addition, the flow of the nanomaterials along the surface of endothelial cells will affect much the chance of
nanomaterials to encounter the tissue cells. In brief, peripheral endothelial cells see
the circulating nanomaterials very infrequently and might almost ignore the
21 Innate Immunity to Nanomaterials
397