PMID- 8695817
OWN - NLM
STAT- MEDLINE
DCOM- 19960905
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 88
IP  - 2
DP  - 1996 Jul 15
TI  - Tumor necrosis factor-alpha and FMLP receptors are functionally linked during 
      FMLP-stimulated activation of adherent human neutrophils.
PG  - 690-6
AB  - Human peripheral blood neutrophils (PMN) plated onto fibrinogen and activated 
      with FMLP release H2O2 and lactoferrin, a specific granule component, with 
      parallel kinetics. Although tumor necrosis factor-alpha (TNF alpha) only primes 
      PMN in suspension, it is a potent agonist of adherent PMN. Activation of adherent 
      PMN by FMLP (10(-7) mol/L) stimulated detectable release of TNF alpha within 45 
      minutes of stimulation, with maximal release (45.5 pg/10(6) cells) detected by 90 
      minutes. TNF alpha release paralleled the release of both lactoferrin and H2O2. 
      To determine if TNF alpha plays a role in H2O2 and lactoferrin release, we 
      investigated the effect of anti-TNF alpha antibodies on FMLP-stimulated 
      activation of adherent PMN. A neutralizing rabbit anti-TNF alpha antibody 
      inhibited both H2O2 and lactoferrin release stimulated by FMLP, whereas rabbit 
      lgG, anti-HLA-A,B,C, anti-CD 14, and anti-interleukin-8 antibodies were without 
      effect. The simultaneous addition of TNF alpha (1,000 U/mL) with anti-TNF alpha 
      antibody reversed the inhibition seen with anti-TNF alpha alone. Furthermore, 
      treatment of PMN with either actinomycin D or cylcoheximide resulted in partial 
      (33%) inhibition of H2O2 and lactoferrin release, suggesting that protein 
      synthesis is required for FMLP-mediated activation of adherent PMN. The addition 
      of TNF alpha to either cycloheximide or of actinomycin D-treated PMN overcame the 
      inhibition, indicating that the effect was specific for TNF alpha. The addition 
      of antibodies against either the 55-or 75-kD TNF alpha receptors (referred to as 
      p55 and p75, respectively) resulted in partial (32%) inhibition of FMLP-mediated 
      activation of H2O2 and lactoferrin release, whereas a combination of both 
      antibodies reduced their release to control levels. These data indicate that both 
      p55 and p75 are involved in FMLP activation of adherent PMN. Taken together, 
      these findings indicate that the production of TNF alpha and ligation of TNF 
      alpha receptors are central to FMLP activation of PMN adherent to fibrinogen.
FAU - Balazovich, K J
AU  - Balazovich KJ
AD  - Department of Pediatrics, University of Michigan School of Medicine, Ann Arbor, 
      MIC, USA.
FAU - Suchard, S J
AU  - Suchard SJ
FAU - Remick, D G
AU  - Remick DG
FAU - Boxer, L A
AU  - Boxer LA
LA  - eng
GR  - AI20065/AI/NIAID NIH HHS/United States
GR  - GM50401/GM/NIGMS NIH HHS/United States
GR  - HL53074/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens, CD)
RN  - 0 (Chemotactic Factors)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (Receptors, Formyl Peptide)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Receptors, Peptide)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type II)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 1CC1JFE158 (Dactinomycin)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 98600C0908 (Cycloheximide)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 3.4.21.- (Lactoferrin)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Animals
MH  - Antigens, CD/physiology
MH  - Chemotactic Factors/*pharmacology
MH  - Cycloheximide/pharmacology
MH  - Dactinomycin/pharmacology
MH  - Humans
MH  - Hydrogen Peroxide/metabolism
MH  - Lactoferrin/metabolism
MH  - N-Formylmethionine Leucyl-Phenylalanine/*pharmacology
MH  - Neutrophils/*drug effects/physiology
MH  - Protein Synthesis Inhibitors/pharmacology
MH  - Rabbits
MH  - Rats
MH  - Receptors, Formyl Peptide
MH  - Receptors, Immunologic/drug effects/*physiology
MH  - Receptors, Peptide/drug effects/*physiology
MH  - Receptors, Tumor Necrosis Factor/physiology
MH  - Receptors, Tumor Necrosis Factor, Type I
MH  - Receptors, Tumor Necrosis Factor, Type II
MH  - Recombinant Proteins/pharmacology
MH  - Respiratory Burst/drug effects
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 1996/07/15 00:00
MHDA- 1996/07/15 00:01
CRDT- 1996/07/15 00:00
PHST- 1996/07/15 00:00 [pubmed]
PHST- 1996/07/15 00:01 [medline]
PHST- 1996/07/15 00:00 [entrez]
AID - S0006-4971(20)63588-1 [pii]
PST - ppublish
SO  - Blood. 1996 Jul 15;88(2):690-6.