Organ
| Receptor expression
| Dextran uptake
|
Liver
| 1) MR: Kupffer cells, LSEC (16)
| 1) Dextran uptake is present in Kupffer cells (39) and in LSEC (40)
|
| 2) L-SIGN, LSECtin: LSEC (31)
| 2) Dextran uptake is present in LSEC (40); dextran uptake is present in liver DCs (41)
|
Spleen
| 1) MR: splenic macrophages, endothelial cells (16)
| 1) Dextran uptake is present in phagocytes (39) and can be presumed according to dextran uptake along capillaries in endothelial cells (42)
|
| 2) SIGN-R1: spleen macrophages (35)
DC-SIGN: spleen DCs (26)
| 2) SIGN-R1-dependent dextran uptake is present in spleen macrophages (35); dextran uptake is present in spleen phagocytes (39) and in spleen DCs (41)
|
Lung
| 1) MR: alveolar macrophages (16)
2) DC-SIGN: alveolar macrophages (25)
| 1, 2) Dextran uptake is present in alveolar macrophages (43)
|
Kidney
| MR: macrophages, glomerular mesangial cells (16)
| Dextran uptake is present in phagocytes (39) and in mesangial cells (44)
|
Heart muscles
| MR: macrophages (16)
| Dextran uptake is present in phagocytes (39)
|
Brain
| MR: retinal microglia cells (45)
| Dextran uptake is present (45)
|
Skin
| MR: dermal microvascular endothelial cells (46)
| Dextran uptake is present (46)
|
Lymphatic system
| 1) MR: endothelial cells of the lymph ducts (47)
| 1) Dextran uptake (or at least binding) seems to be present in lymphatic endothelial cells due to dextran use in visualization of lymph vessels (49-51)
|
| 2) L-SIGN and LSECtin: endothelial cells of the lymph ducts and lymph nodes (31, 48); LSECtin: peripheral blood and thymic DCs (31)
| 2) Dextran uptake or binding seems to be present in lymphatic endothelial cells due to dextran use in visualization of lymph vessels (49, 51)
|
APC
| 1) MR: APCs in skin, muscles, salivary gland, thyroid, pancreas (52)
2) DC-SIGN: human immature MDDCs, mucosal DCs, immature DCs on periphery (skin, tonsils), and mature DCs in lymphoid organs (26); plasmacytoid DC precursors (25); activated B cells (23)
3) Langerin: Langerhans cells
| 1, 2, 3) Dextran uptake is present in human immature MDDCs and Langerhans cells (53), plasmacytoid DCs (54), activated B cells (55)
|
APC, antigen-presenting cell; DC-SIGN, dendritic cell–specific intercellular adhesion molecule (ICAM) 3-grabbing nonintegrin; L-SIGN, liver/lymph node-specific intercellular adhesion molecule (ICAM)-3-grabbing nonintegrin; LSEC, liver sinusoidal endothelial cell; MDDC, monocyte-derived dendritic cell; MR, mannose receptor.
RECEPTOR-DEPENDENT AND INDEPENDENT ENDOCYTOSIS OF DEXTRAN
In the context of possible antimicrobial application of dextran, it is important to note that this molecule can be taken up into the cells. Clinical dextrans (linear molecules with molecular masses 35,000–80,000 that can curculate in the bloodstream from hours to days) are more potent to be taken up into the cells compared to oligodextrans (linear oligomers of a-1,6-linked glucose) (36). The rate of endocytosis is critical for the development of new applications: bigger molecules provide prolonged action and delivery into the cells, while smaller molecules do not provide the receptor clustering and are more potent as the entry inhibitors because they do not induce receptor-dependent endocytosis by themselves.
Dextran is recognized and taken up by macrophages, DCs, LSECs and some other cell types prefferedly via specific receptors (33-36). However dextran can also be taken up via mechanisms of nonspecific fluid-phase endocytosis (FPE). Table 2 specifies the mechanisms of dextran internalization associated with certain cell types and receptors. MR (14) and DC-SIGN (56) participate in the clathrin-mediated endocytosis (CME) mechanism. MRs and DFRs are necessary and sufficient for receptor-mediated dextran uptake in human immature MDDCs (33, 57).