PMID- 12406851
OWN - NLM
STAT- MEDLINE
DCOM- 20030110
LR  - 20220317
IS  - 1073-449X (Print)
IS  - 1073-449X (Linking)
VI  - 166
IP  - 11
DP  - 2002 Dec 1
TI  - Role of interleukin-10 in the intracellular sequestration of human leukocyte 
      antigen-DR in monocytes during septic shock.
PG  - 1475-82
AB  - Monocytes from many critically ill patients show a low level of major 
      histocompatibility complex type II (MHC II) expression. This phenomenon is 
      believed to play a role in these patients' increased susceptibility to secondary 
      infections. In the present study, we show that the level of monocyte human 
      leukocyte antigen (HLA)-DR expression inversely correlates with the degree of 
      severity of the sepsis syndrome. The defect of the monocyte HLA-DR expression 
      resides in an intracellular sequestration of the MHC II molecules, a 
      posttranslational effect. No significant decrease in the rate of transcription of 
      HLA-DR, or its major transcriptional inducer, Class II transactivator, was noted. 
      The levels of HLA-DR protein produced by monocytes from patients with septic 
      shock were comparable to those from healthy volunteers. Plasma from patients with 
      septic shock induced significant HLA-DR endocytosis resulting in decreased 
      surface HLA-DR expression of normal donor monocytes. This effect was partially 
      blocked by anti-interleukin (IL)-10 monoclonal antibody, but not by antagonists 
      to transforming growth factor-beta1, prostaglandins, or beta-adrenergic agonists. 
      Altogether, these data suggest that HLA-DR molecules are re-endocytosed and 
      retained intracellularly in monocytes from patients with septic shock, and that 
      this phenomenon is partially mediated by IL-10. IL-10 may represent a future 
      target for immunomodulating patients with the sepsis syndrome or critically ill 
      patients at risk of developing infections.
FAU - Fumeaux, Thierry
AU  - Fumeaux T
AD  - Department of Internal Medicine, Division of Medical Intensive Care, and Faculty 
      of Medicine, University Hospital of Geneva, Switzerland.
FAU - Pugin, Jerome
AU  - Pugin J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20020815
PL  - United States
TA  - Am J Respir Crit Care Med
JT  - American journal of respiratory and critical care medicine
JID - 9421642
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (RNA, Messenger)
RN  - 130068-27-8 (Interleukin-10)
RN  - EC 3.4.- (Cathepsins)
RN  - EC 3.4.22.27 (cathepsin S)
SB  - IM
CIN - Am J Respir Crit Care Med. 2002 Dec 1;166(11):1417-8. PMID: 12450929
MH  - Adult
MH  - Blotting, Western
MH  - Cathepsins/genetics
MH  - Cell Membrane/metabolism
MH  - Female
MH  - Fluorescent Antibody Technique
MH  - HLA-DR Antigens/*metabolism
MH  - Histocompatibility Antigens Class II/genetics
MH  - Humans
MH  - Interleukin-10/blood/metabolism
MH  - Intracellular Membranes/*metabolism
MH  - Male
MH  - Monocytes/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Shock, Septic/*metabolism/*physiopathology
MH  - Tissue Distribution
EDAT- 2002/10/31 04:00
MHDA- 2003/01/11 04:00
CRDT- 2002/10/31 04:00
PHST- 2002/10/31 04:00 [pubmed]
PHST- 2003/01/11 04:00 [medline]
PHST- 2002/10/31 04:00 [entrez]
AID - 200203-217OC [pii]
AID - 10.1164/rccm.200203-217OC [doi]
PST - ppublish
SO  - Am J Respir Crit Care Med. 2002 Dec 1;166(11):1475-82. doi: 
      10.1164/rccm.200203-217OC. Epub 2002 Aug 15.