PMID- 11321360
OWN - NLM
STAT- MEDLINE
DCOM- 20010920
LR  - 20190921
IS  - 0360-3997 (Print)
IS  - 0360-3997 (Linking)
VI  - 25
IP  - 2
DP  - 2001 Apr
TI  - Evaluation of signal transduction pathways in chemoattractant-induced human 
      monocyte chemotaxis.
PG  - 61-7
AB  - The intracellular signaling pathways involved in human monocyte chemotaxis toward 
      a variety of chemoattractant molecules were evaluated using selected 
      pharmacological agents. Neither phosphatidylinositol-3-kinase (P13K) or 
      extracellular signal-regulated kinase (ERK) activity were required for monocyte 
      migration toward monocyte chemoattractant protein-1 (MCP-1), RANTES (Regulated on 
      Activation, Normal T cell Expressed and Secreted), macrophage inflammatory 
      protein-1alpha (MIP-1alpha) or formyl-Met-Leu-Phe (fMLP), since pretreatment with 
      wortmannin or LY294002, or with PD098059, had no effect on the chemotactic 
      response. Addition of forskolin and IBMX significantly attenuated chemotaxis to 
      each of these chemoattractants and was reversed by co-treatment with Rp-cAMP, a 
      competitive inhibitor of cAMP-dependent protein kinase A. Incubation with the 
      protein kinase C (PKC) inhibitor GF109203X-HCl (GF109) did not affect monocyte 
      migration, but pretreatment of monocytes with PMA significantly impaired the 
      response to each of these chemotactic agents. Inhibition by PMA was reversed by 
      co-treatment with GF109, implying that heterologous PKC activation is capable of 
      desensitizing chemokine and fMLP-induced monocyte chemotaxis. These results help 
      to define the signalling pathways involved in human monocyte chemotaxis and 
      suggest pharmacological approaches to evaluating the cross-desensitization of 
      chemoattractant-induced leukocyte migration.
FAU - Fine, J S
AU  - Fine JS
AD  - Department of Immunology, Schering-Plough Research Institute, Kenilworth, New 
      Jersey, USA.
FAU - Byrnes, H D
AU  - Byrnes HD
FAU - Zavodny, P J
AU  - Zavodny PJ
FAU - Hipkin, R W
AU  - Hipkin RW
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Inflammation
JT  - Inflammation
JID - 7600105
RN  - 0 (Androstadienes)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL3)
RN  - 0 (Chemokine CCL4)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Chemotactic Factors)
RN  - 0 (Chromones)
RN  - 0 (Flavonoids)
RN  - 0 (Macrophage Inflammatory Proteins)
RN  - 0 (Morpholines)
RN  - 1F7A44V6OU (Colforsin)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
RN  - TBT296U68M (1-Methyl-3-isobutylxanthine)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - 1-Methyl-3-isobutylxanthine/pharmacology
MH  - Androstadienes/pharmacology
MH  - Chemokine CCL2/pharmacology
MH  - Chemokine CCL3
MH  - Chemokine CCL4
MH  - Chemokine CCL5/pharmacology
MH  - Chemotactic Factors/*pharmacology
MH  - Chemotaxis, Leukocyte/*drug effects/*physiology
MH  - Chromones/pharmacology
MH  - Colforsin/pharmacology
MH  - Flavonoids/pharmacology
MH  - Humans
MH  - In Vitro Techniques
MH  - Macrophage Inflammatory Proteins/pharmacology
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors/physiology
MH  - Monocytes/*drug effects/*physiology
MH  - Morpholines/pharmacology
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Phosphatidylinositol 3-Kinases/physiology
MH  - Signal Transduction/physiology
MH  - Wortmannin
EDAT- 2001/04/26 10:00
MHDA- 2001/09/21 10:01
CRDT- 2001/04/26 10:00
PHST- 2001/04/26 10:00 [pubmed]
PHST- 2001/09/21 10:01 [medline]
PHST- 2001/04/26 10:00 [entrez]
AID - 10.1023/a:1007152903135 [doi]
PST - ppublish
SO  - Inflammation. 2001 Apr;25(2):61-7. doi: 10.1023/a:1007152903135.