PMID- 8335943
OWN - NLM
STAT- MEDLINE
DCOM- 19930826
LR  - 20131121
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 151
IP  - 3
DP  - 1993 Aug 1
TI  - Characterization of the immunosuppressive effects of nitric oxide in graft vs 
      host disease.
PG  - 1508-18
AB  - The generation of nitric oxide (.N = O) during in vitro assays involving 
      lymphocyte-macrophage interaction can result in profound inhibition of lymphocyte 
      proliferation. The present study examined whether .N = O synthesis plays a role 
      in the suppression observed in immune function assays during graft vs host 
      disease (GvHD). By using a parent to F1 model to induce GvHD (C57BL/6J to 
      C57BL/6J x DBA 2J F1), a mild but transient increase in serum NO2- plus NO3- 
      levels was observed on day 12 after inoculation. Resident peritoneal macrophages 
      obtained from mice with GvHD demonstrated enhanced .N = O synthesis in response 
      to LPS, compared with control F1 peritoneal macrophages. Similarly, when 
      splenocytes from GvHD mice were cultured with Con A or LPS enhanced supernatant 
      NO2- levels were observed, compared with control F1 mice. Addition of 
      NG-monomethyl-L-arginine (NMA), a competitive inhibitor of .N = O synthesis, 
      resulted in decreased NO2- levels and greatly enhanced proliferation in response 
      to Con A. Addition of NMA to LPS-stimulated cultures did not enhance 
      proliferation, perhaps as the result of the paucity of B cells in the GvHD 
      population. LPS-induced .N = O synthesis by GvHD splenocytes was blocked by 
      anti-IFN-gamma mAb, whereas Con A-induced .N = O synthesis was relatively 
      unaffected by similar concentrations of anti-IFN-gamma mAb, suggesting different 
      mechanisms of induction of .N = O synthesis. A proliferative response of 
      splenocytes from mice with GvHD to third-party alloantigen was not detectable, 
      even in the presence of NMA. The suppression observed when splenocytes from GvHD 
      animals were added to control TNP-modified self cultures was partially reversed 
      in the presence of NMA. These results demonstrate that .N = O synthesis in both 
      splenocyte and peritoneal macrophage populations from GvHD mice is enhanced, 
      revealing that in vivo priming of macrophages for .N = O synthesis occurs during 
      GvHD. Some, but not all, in vitro tests of immune function by using GvHD 
      splenocytes are suppressed by the generation of .N = O.
FAU - Hoffman, R A
AU  - Hoffman RA
AD  - Department of Surgery, University of Pittsburgh, PA 15261.
FAU - Langrehr, J M
AU  - Langrehr JM
FAU - Wren, S M
AU  - Wren SM
FAU - Dull, K E
AU  - Dull KE
FAU - Ildstad, S T
AU  - Ildstad ST
FAU - McCarthy, S A
AU  - McCarthy SA
FAU - Simmons, R L
AU  - Simmons RL
LA  - eng
GR  - AI16869/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Nitrates)
RN  - 0 (Nitrites)
RN  - 0 (Trinitrobenzenes)
RN  - 11028-71-0 (Concanavalin A)
RN  - 27JT06E6GR (omega-N-Methylarginine)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 94ZLA3W45F (Arginine)
SB  - IM
MH  - Animals
MH  - Arginine/analogs & derivatives/pharmacology
MH  - Concanavalin A/pharmacology
MH  - Female
MH  - Graft vs Host Disease/*immunology
MH  - *Immune Tolerance
MH  - Lipopolysaccharides/pharmacology
MH  - Lymphocyte Activation/drug effects
MH  - Macrophages/metabolism
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Nitrates/metabolism
MH  - Nitric Oxide/*pharmacology
MH  - Nitrites/metabolism
MH  - Peritoneal Cavity/cytology
MH  - Trinitrobenzenes/immunology
MH  - omega-N-Methylarginine
EDAT- 1993/08/01 00:00
MHDA- 1993/08/01 00:01
CRDT- 1993/08/01 00:00
PHST- 1993/08/01 00:00 [pubmed]
PHST- 1993/08/01 00:01 [medline]
PHST- 1993/08/01 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1993 Aug 1;151(3):1508-18.