corona-protein wrapped PEGylated nanomaterials circulating in a very dilute
concentration which would occur very soon after systemic injection [44].
Immune system would have evolved to handle this naughty situation to enforce
surveillance over the injected circulating nanomaterials as well as invading
organisms. MPS is the expert clearance system and used to make a very slow flow
in the liver, spleen or bone marrow than the usual venous capillaries of every corner
of the periphery of the entire body. Passage of nanomaterials through peripheral
capillaries of these organs are much slow and endow nanomaterials more chance to
interact with endothelial cells, however, these endothelial cells are non-professional
phagocytes [30]. Professional phagocytes are called tissue-resident macrophages
[27, 28], the best-known of which is hepatic macrophages, i.e. Kupffer cells [24,
26]. Kupffer cells reside alongside hepatic sinusoid in association with sinusoidal
endothelial cells in the hepatic column and they comprise about 80% of total bodily
tissue-resident macrophages. Using this location advantage, Kupffer cells are very
prone to check nanomaterials and process and degrade and/or present them to the
immune cells. Roles of hepatic macrophages as phagocytic cells or APCs are now
begun to be understood in detail [26] (Fig. 21.2). Spleen is another organ majoring
in orchestrating immune response, innate and adaptive ones, and their follicles and
germinal centers are performing pivotal role to compartmentalize immune cells
involved in establishing naïve and memorized immune responses to the injected
PEGylated nanomaterials to reach the specific compartment [45]. Spleen’s resident
macrophages will interact with T cells to make helper T cells later to help B cells or
Tc cells. This further paths of responses belong to adaptive immune responses.
Once nanomaterials are engulfed by tissue-resident macrophages, macrophages
process the nanomaterials. The fate of dis-encapsulated, fragmented, degraded
nanomaterials, their cores and coats, or their surface binders and constituents should
have been understood much better, however, dissecting the outcomes of degradation is very difficult and by any chance if ever done, the endeavor to elucidate the
fate would have been laborious. This job reminds the metabolomics, which produces a huge galaxy of data based on the analysis of small molecule drug’s
metabolism.
21.4.2 Kupffer Cells Examine Nanomaterials as Gatekeeper
In normal healthy subjects, liver has heterogeneous macrophages consisting mostly
of embryonal yolk-sac-derived or fetal liver-derived tissue-resident macrophages
and in minor amount of bone marrow monocyte-converted myeloid dendritic cells
[26] (Fig. 21.2). Of course injured liver can have further the monocyte-derived
macrophages, either inflammatory or restorative, and monocytic myeloid-derived
suppressor cells [26]. Alongside the hepatocytes, conventional dendritic cells
(cDC) or plasmacytoid dendritic cells (pDC) reside and have their own
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D. S. Lee and Y. K. Shin
concentration which would occur very soon after systemic injection [44].
Immune system would have evolved to handle this naughty situation to enforce
surveillance over the injected circulating nanomaterials as well as invading
organisms. MPS is the expert clearance system and used to make a very slow flow
in the liver, spleen or bone marrow than the usual venous capillaries of every corner
of the periphery of the entire body. Passage of nanomaterials through peripheral
capillaries of these organs are much slow and endow nanomaterials more chance to
interact with endothelial cells, however, these endothelial cells are non-professional
phagocytes [30]. Professional phagocytes are called tissue-resident macrophages
[27, 28], the best-known of which is hepatic macrophages, i.e. Kupffer cells [24,
26]. Kupffer cells reside alongside hepatic sinusoid in association with sinusoidal
endothelial cells in the hepatic column and they comprise about 80% of total bodily
tissue-resident macrophages. Using this location advantage, Kupffer cells are very
prone to check nanomaterials and process and degrade and/or present them to the
immune cells. Roles of hepatic macrophages as phagocytic cells or APCs are now
begun to be understood in detail [26] (Fig. 21.2). Spleen is another organ majoring
in orchestrating immune response, innate and adaptive ones, and their follicles and
germinal centers are performing pivotal role to compartmentalize immune cells
involved in establishing naïve and memorized immune responses to the injected
PEGylated nanomaterials to reach the specific compartment [45]. Spleen’s resident
macrophages will interact with T cells to make helper T cells later to help B cells or
Tc cells. This further paths of responses belong to adaptive immune responses.
Once nanomaterials are engulfed by tissue-resident macrophages, macrophages
process the nanomaterials. The fate of dis-encapsulated, fragmented, degraded
nanomaterials, their cores and coats, or their surface binders and constituents should
have been understood much better, however, dissecting the outcomes of degradation is very difficult and by any chance if ever done, the endeavor to elucidate the
fate would have been laborious. This job reminds the metabolomics, which produces a huge galaxy of data based on the analysis of small molecule drug’s
metabolism.
21.4.2 Kupffer Cells Examine Nanomaterials as Gatekeeper
In normal healthy subjects, liver has heterogeneous macrophages consisting mostly
of embryonal yolk-sac-derived or fetal liver-derived tissue-resident macrophages
and in minor amount of bone marrow monocyte-converted myeloid dendritic cells
[26] (Fig. 21.2). Of course injured liver can have further the monocyte-derived
macrophages, either inflammatory or restorative, and monocytic myeloid-derived
suppressor cells [26]. Alongside the hepatocytes, conventional dendritic cells
(cDC) or plasmacytoid dendritic cells (pDC) reside and have their own
398
D. S. Lee and Y. K. Shin