PMID- 8943888
OWN - NLM
STAT- MEDLINE
DCOM- 19970117
LR  - 20190705
IS  - 0007-1048 (Print)
IS  - 0007-1048 (Linking)
VI  - 95
IP  - 3
DP  - 1996 Dec
TI  - Signalling defect in FMLP-induced neutrophil respiratory burst in myelodysplastic 
      syndromes.
PG  - 482-8
AB  - Myelodysplastic syndromes (MDS) are clonal haematological disorders and MDS 
      neutrophils have various abnormal functions which cause an increased risk of 
      infective mortality. We examined luminol-dependent chemiluminescence and 
      cytoplasmic Ca2+ increase in order to characterize the mechanisms of a signalling 
      defect in MDS neutrophil respiratory burst. In MDS patients, chemiluminescence 
      stimulated with N-formyl-L-methionyl-L-leucil-L-phenylalanine (FMLP) and calcium 
      ionophore A23187 was defective (17.2 +/- 13.7 v 44.3 +/- 16.6, P = 0.001; 42.2 
      +/- 21.3 v 82.0 +/- 23.6, P < 0.05, respectively), but phorbol 12-myristate 
      13-acetate (PMA) chemiluminescence was normal (73.4 +/- 26.9 v 79.5 +/- 23.8, P = 
      0.52). There were no statistical significances in cytoplasmic Ca2+ increase 
      stimulated with FMLP and recombinant human interleukin-8 (rhIL-8) compared with 
      controls (251.1 +/- 104.3 v 272.7 +/- 41.2, P = 0.295; 238.6 +/- 65.0 v 253.9 +/- 
      38.3, P = 0.567, respectively). Flow cytometric analysis of MDS neutrophils 
      disclosed that most MDS patients showed normal neutrophil cytoplasmic Ca2+ 
      response to FMLP and rhIL-8. However, two patients with refractory anaemia with 
      excess of blasts displayed a significant decrease of both chemiluminescence and 
      cytoplasmic Ca2+ response to FMLP, and they also displayed low expression of FMLP 
      receptor. These data suggest that most MDS patients have low FMLP 
      chemiluminescence which is not due to a defect in the FMLP receptor. It is 
      proposed that defective FMLP chemiluminescence in MDS results from a putative 
      defect in protein kinase C- and Ca(2+)-independent cell-signalling mechanisms. 
      Only a small group of patients have numerical or structural defects in the FMLP 
      receptor, causing significant decrease of neutrophil respiratory burst.
FAU - Nakaseko, C
AU  - Nakaseko C
AD  - Second Department of Internal Medicine, Chiba University, School of Medicine, 
      Japan.
FAU - Asai, T
AU  - Asai T
FAU - Wakita, H
AU  - Wakita H
FAU - Oh, H
AU  - Oh H
FAU - Saito, Y
AU  - Saito Y
LA  - eng
PT  - Journal Article
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (Interleukin-8)
RN  - 0 (Receptors, Formyl Peptide)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Receptors, Peptide)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcium/metabolism
MH  - Flow Cytometry
MH  - Humans
MH  - Interleukin-8/pharmacology
MH  - Luminescent Measurements
MH  - Myelodysplastic Syndromes/*metabolism
MH  - N-Formylmethionine Leucyl-Phenylalanine/*pharmacology
MH  - Neutrophils/*metabolism
MH  - Receptors, Formyl Peptide
MH  - Receptors, Immunologic/metabolism
MH  - Receptors, Peptide/metabolism
MH  - *Respiratory Burst
EDAT- 1996/12/01 00:00
MHDA- 1996/12/01 00:01
CRDT- 1996/12/01 00:00
PHST- 1996/12/01 00:00 [pubmed]
PHST- 1996/12/01 00:01 [medline]
PHST- 1996/12/01 00:00 [entrez]
AID - 10.1111/j.1365-2141.1996.tb08992.x [doi]
PST - ppublish
SO  - Br J Haematol. 1996 Dec;95(3):482-8. doi: 10.1111/j.1365-2141.1996.tb08992.x.