PMID- 11154208
OWN - NLM
STAT- MEDLINE
DCOM- 20010315
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 97
IP  - 2
DP  - 2001 Jan 15
TI  - HIV-1 Tat promotes monocyte chemoattractant protein-1 secretion followed by 
      transmigration of monocytes.
PG  - 352-8
AB  - The mechanism whereby HIV-infected cells transit from the bloodstream into 
      tissues is not well defined. This phenomenon was addressed by studying the 
      effects of HIV-1 Tat, a protein secreted by infected cells, on human lung 
      microvascular endothelial cells (HMVEC-Ls). It was found that monocyte 
      chemoattractant protein-1 (MCP-1) was released from HMVEC-Ls in a dose- and 
      time-dependent manner after Tat treatment. MCP-1 is a potent beta-chemokine that 
      recruits monocytes and T cells and promotes cell adhesion and transmigration 
      across an endothelial monolayer. It was also observed that MCP-1 and the culture 
      medium from Tat-treated HMVEC-Ls were chemotactic for CD14(+) monocytes from 
      human peripheral blood and for THP-1, a promonocytic cell line used as a model 
      system. To characterize the signaling pathways underlying the observed induction 
      of MCP-1, HMVEC-Ls were treated with 2 different protein kinase inhibitors: 
      PD98059, a MAP kinase inhibitor, and GF109203X, a protein kinase C (PKC) 
      inhibitor. MCP-1 release was significantly reduced when PKC was inhibited, and 
      slightly decreased when PI3 kinase was blocked; no effect on MCP-1 release was 
      observed on MAP kinase inhibition. Similarly, transmigration of THP-1 cells was 
      significantly impaired by the PKC inhibitor, but not by the other tested 
      inhibitors. These data indicate that the HIV-1 Tat protein may act as a 
      protocytokine by causing the release of MCP-1 from the endothelial monolayer, and 
      thereby facilitating monocyte transmigration into tissues via a PKC signaling 
      pathway.
FAU - Park, I W
AU  - Park IW
AD  - Division of Experimental Medicine and Hematology/Oncology, Beth Israel Deaconess 
      Medical Center, Harvard Institutes of Medicine, Boston, MA 02115, USA.
FAU - Wang, J F
AU  - Wang JF
FAU - Groopman, J E
AU  - Groopman JE
LA  - eng
GR  - HL53745/HL/NHLBI NIH HHS/United States
GR  - HL61940/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 (Chemokine CCL2)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (Gene Products, tat)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (Receptors, Growth Factor)
RN  - 0 (tat Gene Products, Human Immunodeficiency Virus)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Cell Culture Techniques
MH  - Cell Movement/drug effects
MH  - Chemokine CCL2/*metabolism
MH  - Chemotaxis
MH  - Culture Media, Conditioned/chemistry
MH  - Dose-Response Relationship, Drug
MH  - Endothelium, Vascular/cytology
MH  - Enzyme Activation/drug effects
MH  - Extracellular Matrix Proteins/metabolism
MH  - Gene Products, tat/*pharmacology/physiology
MH  - HIV-1/*chemistry
MH  - Humans
MH  - Lipopolysaccharide Receptors
MH  - MAP Kinase Signaling System/drug effects
MH  - Microcirculation/cytology
MH  - Monocytes/*cytology/drug effects/immunology
MH  - Phosphorylation/drug effects
MH  - Protein Kinase C/drug effects/metabolism/physiology
MH  - Receptor Protein-Tyrosine Kinases/metabolism
MH  - Receptors, Growth Factor/metabolism
MH  - Receptors, Vascular Endothelial Growth Factor
MH  - Signal Transduction
MH  - tat Gene Products, Human Immunodeficiency Virus
EDAT- 2001/01/12 11:00
MHDA- 2001/03/17 10:01
CRDT- 2001/01/12 11:00
PHST- 2001/01/12 11:00 [pubmed]
PHST- 2001/03/17 10:01 [medline]
PHST- 2001/01/12 11:00 [entrez]
AID - S0006-4971(20)65996-1 [pii]
AID - 10.1182/blood.v97.2.352 [doi]
PST - ppublish
SO  - Blood. 2001 Jan 15;97(2):352-8. doi: 10.1182/blood.v97.2.352.