Table 2.
The effect of HA and HA fragments on macrophages and dendritic cells.
| Cell type | HA size (kDa) | HA source | Effect | Molecule | Steps to exclude LPS | Reference |
|---|---|---|---|---|---|---|
| MACROPHAGES AND MONOCYTES | ||||||
| BMDM | 40–80 | Bovine trachea | Induced IL-1β, TNFα mRNA | CD44 | Used LPS hyporesponsive mouse | (106) |
| BMDM and MH-S cell line | 6000 | Rooster comb | No effect | – | Not specified | (107) |
| 474, 267 | Sonicated | Activated NFκβ | ||||
| MH-S cell line and human inflammatory alveolar Mϕ | 6000 | Rooster comb | No effect | CD44 | Endotoxin tested, polymyxin added | (109) |
| 470 | Sonicated | Induced MIP1α, MIP1β, IP-10, RANTES, MCP-1 mRNA in mouse and IL-8 in human | ||||
| 280 | Human umbilical cord | |||||
| 35 | ||||||
| 6 mer | Rooster comb | |||||
| 2 mer | Not specified | No effect | ||||
| MH-S cell line, BMDM | 200 | Human umbilical cord | Induced iNOS mRNA | Used LPS hyporesponsive mouse, polymyxin added | (108) | |
| Activated NFκβ | ||||||
| Elicited peritoneal Mϕ | 280 | Human umbilical cord | MIP1α, MIP1β, RANTES, IL-12 mRNA | Used LPS hyporesponsive mouse, endotoxin present, polymyxin added | (115) | |
| Peritoneal Mϕ | 135 | Digested from bacterial HA | Induced MIP-2 and TNFα | TLR2 | CD44, TLR2/4 KO mice. Endotoxin tested (<40 pg/mg HA), Hyal digestion, polymyxin added | (112) |
| TLR4 | ||||||
| 200 | Patient seruma | Induced MIP-2, MIP1α, KC | Not CD44 | |||
| Elicited peritoneal Mϕ | 6000 | Rooster comb | No effect | – | Used LPS hyporesponsive mouse, endotoxin tested solutions, polymyxin added | (111) |
| 200 | Human umbilical cord | Induced MIP1α, MIP1β, KC, MCP-1, RANTES, TNFα mRNA | TLR2 | |||
| MH-S cell line and human THP-1 cell line | Not specified | Human umbilical cord | Induced MIP-2, TNF α, GM-csf, RANTES IL-1α, and Mmp13, Tgfb2 mRNA, and IL-8 (human) | CD44 | Endotoxin removed, DNA free | (113) |
| TLR4 | ||||||
| MH-S cell line and elicited peritoneal Mϕ | 200 | Human umbilical cord | Induced TNFα and KC secretion | – | Used LPS hyporesponsive mouse | (116) |
| MH-S cell line and elicited peritoneal Mϕ | 500–730 | Rooster comb | No effect | CD44 | Used a LPS hyporesponsive mouse, Hyal digestion, endotoxin removal | (114) |
| Up to 500 | Human umbilical cord | Induced MIP-2 and pro-IL-1β via TLR4. Induced IL-1β via CD44, Hyals and NLRP3 | TLR4 | |||
| NLRP3 | ||||||
| 4–18 mers | Not specified | Induced MIP-2 | ||||
| Raw264 and MH-S cell line | Specific sizes 11–970 | Acid hydrolysis of bacterial HA | No effect on NO or TNFα | – | Endotoxin tested <0.01 EU/ml | (117) |
| DENDRITIC CELLS | ||||||
| BMDC, human blood-derived DCs | 1000 | Rooster comb, sonicated | No effect | – | Endotoxin tested (<0.06 EU/ml or <0.1 ng/ml LPS), polymyxin added | (29, 30) |
| 80–200 | ||||||
| 4–14 mers | Hyal digestion of sonicated HA | Induced HLR-DR expression and IL-1β, TNFα, IL-12. Activated NFκβ. Activated MAPK/p38 and NFκβ | TLR4 not CD44 or RHAMM | |||
| BMDC | >570 | Not specified | Upregulated CD40, CD80, CD86 | Not CD44 | Polymyxin added | (74) |
| BMDC | 200 | Human umbilical cord | Induced MIP1α | Used LPS hyporesponsive mouse, polymyxin added | (111) | |
| BMDC | 2–12 mers | Commercial source | Unable to activate DCs in vitro | – | – | (118) |
All cells are murine unless otherwise stated.
BMDM and BMDC, bone marrow-derived macrophages and dendritic cells, respectively; Mϕ, macrophages; Hyal, hyaluronidase. MIP-2 and KC are also known as CXCL2 and CXCL1, respectively.
aPatient serum was from patients with acute lung injury. Items in blue indicate no proinflammatory effect was observed with HA.