PMID- 12662298
OWN - NLM
STAT- MEDLINE
DCOM- 20030424
LR  - 20190818
IS  - 0300-9475 (Print)
IS  - 0300-9475 (Linking)
VI  - 57
IP  - 4
DP  - 2003 Apr
TI  - A novel function for chemokines: downregulation of neutrophil migration.
PG  - 350-61
AB  - Migration is a key function of stem cells during ontogenesis, of fibroblasts in 
      wound healing and of immune cells in host defence. The signals that initiate 
      migration are as important as signals that terminate migration, once the 
      destination has been reached. We now show that 
      formyl-methionyl-leucyl-phenylalanine (fMLP)-induced migration of neutrophils was 
      inhibited by increasing concentrations of interleukin-8 (IL-8). IL-8 dose 
      dependently increased the frequency and the duration of stop-periods, whereas the 
      percentage of cells of a population that was locomotory active remained constant. 
      The stop-signal delivered by IL-8 was intracellularly transduced by a dichotomic 
      pathway: (i) the activation of the adenylyl cyclase leads to an increase of 
      cytosolic cyclic adenosine monophosphate, which results in an activation of the 
      sarcoplasmatic/endoplasmatic reticulum calcium ATPase pump and a calcium 
      sequestration; (ii) the activation of the phospholipase Cbeta (PLCbeta) generates 
      inositol-1,4,5-phosphate (IP3) and diacylglycerol (DAG), which results in 
      IP3-mediated release of intracellularly stored calcium in the endoplasmatic 
      reticulum and DAG-mediated activation of protein kinase C. Thus, we show for the 
      first time that a chemokine, IL-8, in concert with fMLP, downregulates the 
      neutrophil migration through the regulation of the intracellular calcium 
      concentration via the adenylyl cyclase and the PLCbeta2.
FAU - Lang, K
AU  - Lang K
AD  - Institute for Immunology, Witten/Herdecke University, Stockumer Strasse 10, 58448 
      Witten, Germany.
FAU - Hatt, H
AU  - Hatt H
FAU - Niggemann, B
AU  - Niggemann B
FAU - Zaenker, K S
AU  - Zaenker KS
FAU - Entschladen, F
AU  - Entschladen F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Scand J Immunol
JT  - Scandinavian journal of immunology
JID - 0323767
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Interleukin-8)
RN  - 0 (Naphthalenes)
RN  - 0 (Tyrphostins)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 63X7MBT2LQ (Bucladesine)
RN  - I271P23G24 (calphostin C)
RN  - RV0GCD31OJ (tyrphostin A23)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Bucladesine/pharmacology
MH  - Calcium/immunology/metabolism
MH  - Cell Adhesion/immunology
MH  - Chemotaxis, Leukocyte/drug effects/*immunology
MH  - Down-Regulation/immunology
MH  - Enzyme Inhibitors/pharmacology
MH  - Humans
MH  - Interleukin-8/*immunology/metabolism/pharmacology
MH  - Microscopy, Confocal
MH  - Microscopy, Video
MH  - N-Formylmethionine Leucyl-Phenylalanine/antagonists & 
      inhibitors/*immunology/pharmacology
MH  - Naphthalenes/pharmacology
MH  - Neutrophils/cytology/*immunology
MH  - Signal Transduction/immunology
MH  - Surface Plasmon Resonance
MH  - Tyrphostins/pharmacology
EDAT- 2003/03/29 05:00
MHDA- 2003/04/25 05:00
CRDT- 2003/03/29 05:00
PHST- 2003/03/29 05:00 [pubmed]
PHST- 2003/04/25 05:00 [medline]
PHST- 2003/03/29 05:00 [entrez]
AID - 1247 [pii]
AID - 10.1046/j.1365-3083.2003.01247.x [doi]
PST - ppublish
SO  - Scand J Immunol. 2003 Apr;57(4):350-61. doi: 10.1046/j.1365-3083.2003.01247.x.