PMID- 11460314
OWN - NLM
STAT- MEDLINE
DCOM- 20011212
LR  - 20191105
IS  - 1567-5769 (Print)
IS  - 1567-5769 (Linking)
VI  - 1
IP  - 7
DP  - 2001 Jul
TI  - Mechanisms and modulation of formyl-methionyl-leucyl-phenylalanine (fMLP)-induced 
      Ca2+ mobilization in human neutrophils.
PG  - 1341-9
AB  - The effect of fMLP (N-formyl-methionyl-leucyl-phenylalanine), a 
      neutrophil-stimulating bacterial peptide, on Ca2+ mobilization in human 
      neutrophils was examined using fura-2 as a Ca2+ indicator. fMLP (10 nM-10 microM) 
      increased [Ca2+]i concentration-dependently. The [Ca2+]i signal comprised an 
      initial rise followed by a gradual decay and a sustained phase. External Ca2+ 
      removal partly decreased the signal. La3+ (50 microM) pretreatment mimicked the 
      effect of Ca2+ removal. In Ca(2+)-free medium, pretreatment with 1 microM 
      thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) prevented 10 microM 
      fMLP from increasing [Ca2+]i; whereas 1 microM thapsigargin still significantly 
      increased [Ca2+]i after pretreatment with 10 microM fMLP. Addition of 3 mM Ca2+ 
      induced a concentration-dependent [Ca2+]i increase after pretreatment with fMLP 
      in Ca(2+)-free medium. This Ca2+ entry was partly inhibited by econazole (25 
      microM), SKF96365 (50 microM), and a phospholipase A2 inhibitor (aristolochic 
      acid; 20 microM). The fMLP (10 microM)-induced Ca2+ release was abolished by 
      inhibiting phospholipase C with 2 microM U73122. The fMLP-induced [Ca2+]i 
      increase was inhibited by 25% by pretreatment with 10 nM phorbol ester to 
      activate protein kinase C but was augmented by 27% by pretreatment with 2 microM 
      GF 109203X to inactivate protein kinase C. We found that fMLP increase reactive 
      oxygen intermediate (ROI) production in neutrophils, which can be suppressed by 
      U73122 pretreatment. Collectively, this study shows that in human neutrophils, 
      fMLP increased [Ca2+]i concentration-dependently by releasing Ca2+ from 
      phospholipase C-coupled, thapsigargin-sensitive stores, accompanied by Ca2+ 
      entry. The fMLP-induced [Ca2+]i rise was modulated by protein kinase C, and the 
      fMLP-induced Ca2+ entry was abolished by La3+, and was reduced by econazole, 
      SKF96365 and inhibition of phospholipase A2.
FAU - Chen, L W
AU  - Chen LW
AD  - Department of Surgery, Kaohsiung Veterans General Hospital, 386 Ta Chung 1st Rd., 
      Kaohsiung 813, Taiwan.
FAU - Jan, C R
AU  - Jan CR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Reactive Oxygen Species)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 6I3K30563S (Lanthanum)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 3.1.4.- (Type C Phospholipases)
RN  - SY7Q814VUP (Calcium)
RN  - TSN3DL106G (Fura-2)
SB  - IM
MH  - Calcium/*metabolism
MH  - Calcium Signaling/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Fluorescent Dyes
MH  - Fura-2
MH  - Humans
MH  - In Vitro Techniques
MH  - Lanthanum/pharmacology
MH  - N-Formylmethionine Leucyl-Phenylalanine/*pharmacology
MH  - Neutrophils/drug effects/*metabolism
MH  - Protein Kinase C/antagonists & inhibitors
MH  - Reactive Oxygen Species
MH  - Type C Phospholipases/antagonists & inhibitors
EDAT- 2001/07/20 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/07/20 10:00
PHST- 2001/07/20 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/07/20 10:00 [entrez]
AID - S1567-5769(01)00066-2 [pii]
AID - 10.1016/s1567-5769(01)00066-2 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2001 Jul;1(7):1341-9. doi: 10.1016/s1567-5769(01)00066-2.