findings were in normal individuals. These colloids were redistributed to the spleen
and the bone marrow in chronic liver diseases, especially in liver cirrhosis [29].
Kupffer cells and hepatocytes in the liver competes for the clearing of the
extraneous molecules such as biomacromolecules or larger particulate materials as
well as small molecules from the circulation. These extraneous molecules, if they
are trapped in colloids and escaped the size filter of pulmonary capillary flow, meet
circulating humoral mediators of antibodies or pentraxins [4] or circulating innate
immune cells [17]. They can act as hapten, make opsonin, activate complement
system, make circulating immune complex and further again phagocytosed by
macrophages or trapped by neutrophil extracellular trap (NET) in the localized
inflammation sites by neutrophils by neutrophil extracellular trap, and presented
again to adaptive immune cells to elicit further production of antibodies or retaliation by cytotoxic T cells [10, 11]. This continues repetitiously until resolution.
Among these complicated purposeful surveillance system, Kupffer cells take
important roles to remove most of the injected foreign materials [8, 23, 25].
Considering their high proportion among MPS and easy accessibility from both the
intestines via portal vein and the systemic circulation via hepatic artery, Kupffer
cells do the role of gatekeeping [8]. Any infective living or injected non-living
materials should pass this toll. In this line of reasoning, systemically injected
therapeutic monoclonal antibodies were considered to be mostly processed in the
liver especially by Kupffer cells.
By the way, the roles of hepatocytes to metabolize and excrete the extraneous
small molecules have been very well-known as detoxification. The fate of nanomaterials, if injected systemically via intravenous routes, are up to the disposal of
differential participation of hepatocytes and Kupffer cells. While hepatocytes are
mainly using hepatobiliary excretion system sometimes using the help of bile acids,
Kupffer cells act as tissue-resident macrophages [27, 28], stationary to maintain the
removal process interacting closely with innate or adaptive immune system. How
these two cells collaborate with each other or these two cells collaborate with
endothelial cells or other minor liver cells are recently reported [30]. Macrophages
can redirect non-professional phagocytes such as endothelial cells to phagocytes.
Among the 20% of non-parenchymal cells of the liver, endothelial cells occupying
50% of these non-parenchymal cells do phagocytize invading or injected materials,
animate or inanimate, under the direction of Kupffer cells occupying the other 20%
of non-parenchymal cells of the liver.
Tissue macrophages of the spleen are also the major player to eradicate the
foreign infectious and injected materials. As capillary size is 5–10 lm, materials
less than this size reach spleen as well as liver, and spleen weighs 150 g just 1/10 of
the liver and taking up the same equivalent of Tc-99m colloid in colloid liver-spleen
scan. In the sinusoid of the spleen, the infective and injected materials meet immune
cells of innate immunity and adaptive immunity. They need to evade immune
response to circulate further in systemic circulation and also they might modulate
innate immune response as well as activate naïve T cells. Pretending-self strategy of
infective or injected materials was reported. While infectious agents have developed
this strategy by evolutionary processes, recent investigation has tried to use
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D. S. Lee and Y. K. Shin
and the bone marrow in chronic liver diseases, especially in liver cirrhosis [29].
Kupffer cells and hepatocytes in the liver competes for the clearing of the
extraneous molecules such as biomacromolecules or larger particulate materials as
well as small molecules from the circulation. These extraneous molecules, if they
are trapped in colloids and escaped the size filter of pulmonary capillary flow, meet
circulating humoral mediators of antibodies or pentraxins [4] or circulating innate
immune cells [17]. They can act as hapten, make opsonin, activate complement
system, make circulating immune complex and further again phagocytosed by
macrophages or trapped by neutrophil extracellular trap (NET) in the localized
inflammation sites by neutrophils by neutrophil extracellular trap, and presented
again to adaptive immune cells to elicit further production of antibodies or retaliation by cytotoxic T cells [10, 11]. This continues repetitiously until resolution.
Among these complicated purposeful surveillance system, Kupffer cells take
important roles to remove most of the injected foreign materials [8, 23, 25].
Considering their high proportion among MPS and easy accessibility from both the
intestines via portal vein and the systemic circulation via hepatic artery, Kupffer
cells do the role of gatekeeping [8]. Any infective living or injected non-living
materials should pass this toll. In this line of reasoning, systemically injected
therapeutic monoclonal antibodies were considered to be mostly processed in the
liver especially by Kupffer cells.
By the way, the roles of hepatocytes to metabolize and excrete the extraneous
small molecules have been very well-known as detoxification. The fate of nanomaterials, if injected systemically via intravenous routes, are up to the disposal of
differential participation of hepatocytes and Kupffer cells. While hepatocytes are
mainly using hepatobiliary excretion system sometimes using the help of bile acids,
Kupffer cells act as tissue-resident macrophages [27, 28], stationary to maintain the
removal process interacting closely with innate or adaptive immune system. How
these two cells collaborate with each other or these two cells collaborate with
endothelial cells or other minor liver cells are recently reported [30]. Macrophages
can redirect non-professional phagocytes such as endothelial cells to phagocytes.
Among the 20% of non-parenchymal cells of the liver, endothelial cells occupying
50% of these non-parenchymal cells do phagocytize invading or injected materials,
animate or inanimate, under the direction of Kupffer cells occupying the other 20%
of non-parenchymal cells of the liver.
Tissue macrophages of the spleen are also the major player to eradicate the
foreign infectious and injected materials. As capillary size is 5–10 lm, materials
less than this size reach spleen as well as liver, and spleen weighs 150 g just 1/10 of
the liver and taking up the same equivalent of Tc-99m colloid in colloid liver-spleen
scan. In the sinusoid of the spleen, the infective and injected materials meet immune
cells of innate immunity and adaptive immunity. They need to evade immune
response to circulate further in systemic circulation and also they might modulate
innate immune response as well as activate naïve T cells. Pretending-self strategy of
infective or injected materials was reported. While infectious agents have developed
this strategy by evolutionary processes, recent investigation has tried to use
396
D. S. Lee and Y. K. Shin