PMID- 8615864
OWN - NLM
STAT- MEDLINE
DCOM- 19960606
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 50
IP  - 11
DP  - 1995 Nov 27
TI  - Adenosine modulation of tumor necrosis factor-alpha-induced neutrophil 
      activation.
PG  - 1851-7
AB  - We hypothesized that adenosine, known to be release from inflammatory sites, 
      could lessen the potentially damaging activity of neutrophils (PMN) primed by 
      tumor necrosis factor-alpha (TNF alpha) at sites of infection. We investigated 
      the effect of adenosine on PMN primed with cell-free medium from mononuclear 
      leukocytes (MNL) that had been treated with lipopolysaccharide (LPS) yielding a 
      conditioned medium rich in TNF alpha and on PMN primed with recombinant human TNF 
      alpha (rhTNF alpha). LPS (10 ng/mL) minimally primed PMN, but LPS-MNL-conditioned 
      medium increased PMN chemiluminescence in response to f-Met-Leu-Phe (fMLP) 1242% 
      compared with unprimed PMN. LPS-MNL-conditioned medium contained adenosine 
      (approximately 30 nM). Converting the adenosine in the LPS-MNL-conditioned medium 
      to inosine with adenosine deaminase (ADA) or blocking adenosine binding to PMN 
      with the adenosine receptor antagonist 
      1,3-dipropyl-8-(phenyl-p-acrylate)-xanthine (BW A1433U) resulted in a near 
      doubling of chemiluminescence. The LPS-MNL-conditioned medium contained TNF alpha 
      (836 pg/mL; approximately 1 U/mL). Recombinant human TNF alpha (1 U/mL) primed 
      PMN for a 1033% increase in chemiluminescence. Added adenosine decreased rhTNF 
      alpha-primed PMN chemiluminescence (IC50 approximately 100 nM), and adenosine 
      (100 nM) decreased both superoxide and myeloperoxidase release from rhTNF 
      alpha-primed fMLP-stimulated PMN. The activity of adenosine was counteracted by 
      ADA and BW A1433U, and the modulating effect of adenosine was on the primed 
      response rather than on priming per se. Thus, physiological concentrations of 
      adenosine reduce the effects of recombinant human TNF alpha and native human TNF 
      alpha (released from LPS-treated MNL) on PMN activity. Endogenous adenosine may 
      preclude or minimize damage to infected tissue by damping the TNF alpha-primed 
      PMN oxidative response.
FAU - Barnes, C R
AU  - Barnes CR
AD  - Department of Medicine, University of Virginia, Charlottesville 22908, USA.
FAU - Mandell, G L
AU  - Mandell GL
FAU - Carper, H T
AU  - Carper HT
FAU - Luong, S
AU  - Luong S
FAU - Sullivan, G W
AU  - Sullivan GW
LA  - eng
GR  - R01AI09504/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 11062-77-4 (Superoxides)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - EC 1.11.1.7 (Peroxidase)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - Adenosine/*pharmacology
MH  - Adjuvants, Immunologic/*pharmacology
MH  - Culture Media, Conditioned
MH  - Humans
MH  - Leukocytes, Mononuclear/metabolism
MH  - Lipopolysaccharides
MH  - Luminescent Measurements
MH  - N-Formylmethionine Leucyl-Phenylalanine
MH  - Neutrophil Activation/*drug effects
MH  - Neutrophils/*drug effects/metabolism
MH  - Peroxidase/metabolism
MH  - Recombinant Proteins/pharmacology
MH  - Respiratory Burst/drug effects
MH  - Superoxides/metabolism
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1995/11/27 00:00
MHDA- 1995/11/27 00:01
CRDT- 1995/11/27 00:00
PHST- 1995/11/27 00:00 [pubmed]
PHST- 1995/11/27 00:01 [medline]
PHST- 1995/11/27 00:00 [entrez]
AID - 0006-2952(95)02078-0 [pii]
AID - 10.1016/0006-2952(95)02078-0 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 1995 Nov 27;50(11):1851-7. doi: 10.1016/0006-2952(95)02078-0.