PMID- 17049055
OWN - NLM
STAT- MEDLINE
DCOM- 20061121
LR  - 20230124
IS  - 1600-6135 (Print)
IS  - 1600-6135 (Linking)
VI  - 6
IP  - 11
DP  - 2006 Nov
TI  - The role of hyaluronan degradation products as innate alloimmune agonists.
PG  - 2622-35
AB  - Dendritic cells (DCs) play a key role in initiating alloimmunity yet the 
      substances that activate them during the host response to transplantation remain 
      elusive. In this study we examined the potential roles of endogenous innate 
      immune agonists in activating dendritic cell-dependent alloimmunity. Using a 
      murine in vitro culture system, we show that 135 KDa fragments of the 
      extracellular matrix glycosaminoglycan hyaluronan induce dendritic cell 
      maturation and initiate alloimmunity. Priming of alloimmunity by 
      hyaluronan-activated DCs was dependent on signaling via TIR-associated protein, a 
      Toll-like receptor (TLR) adaptor downstream of TLRs 2 and 4. However, this effect 
      was independent of alternate TLR adaptors, MyD88 or Trif. Using an in vivo murine 
      transplant model, we show that hyaluronan accumulated during skin transplant 
      rejection. Examination of human lung transplant recipients demonstrated that 
      increased levels of intragraft hyaluronan were associated with bronchiolitis 
      obliterans syndrome. In conclusion, our study suggests that fragments of 
      hyaluronan can act as innate immune agonists that activate alloimmunity.
FAU - Tesar, B M
AU  - Tesar BM
AD  - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale 
      University School of Medicine, New Haven CT, Connecticut, USA.
FAU - Jiang, D
AU  - Jiang D
FAU - Liang, J
AU  - Liang J
FAU - Palmer, S M
AU  - Palmer SM
FAU - Noble, P W
AU  - Noble PW
FAU - Goldstein, D R
AU  - Goldstein DR
LA  - eng
GR  - AI052201/AI/NIAID NIH HHS/United States
GR  - HL060539/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Transplant
JT  - American journal of transplantation : official journal of the American Society of 
      Transplantation and the American Society of Transplant Surgeons
JID - 100968638
RN  - 0 (Isoantigens)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Oligosaccharides)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Toll-Like Receptor 8)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9004-61-9 (Hyaluronic Acid)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Dendritic Cells/*immunology
MH  - Hyaluronic Acid/*immunology/metabolism/pharmacology
MH  - Inflammation/physiopathology
MH  - Isoantigens/*immunology
MH  - Lung Transplantation/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myeloid Differentiation Factor 88/deficiency/genetics/physiology
MH  - Oligosaccharides/*immunology/pharmacology
MH  - Skin Transplantation/*immunology
MH  - Toll-Like Receptor 4/immunology
MH  - Toll-Like Receptor 8/immunology
MH  - Tumor Necrosis Factor-alpha/biosynthesis
EDAT- 2006/10/20 09:00
MHDA- 2006/12/09 09:00
CRDT- 2006/10/20 09:00
PHST- 2006/10/20 09:00 [pubmed]
PHST- 2006/12/09 09:00 [medline]
PHST- 2006/10/20 09:00 [entrez]
AID - S1600-6135(22)02871-4 [pii]
AID - 10.1111/j.1600-6143.2006.01537.x [doi]
PST - ppublish
SO  - Am J Transplant. 2006 Nov;6(11):2622-35. doi: 10.1111/j.1600-6143.2006.01537.x.