PMID- 16530182
OWN - NLM
STAT- MEDLINE
DCOM- 20060731
LR  - 20091119
IS  - 0014-4827 (Print)
IS  - 0014-4827 (Linking)
VI  - 312
IP  - 10
DP  - 2006 Jun 10
TI  - Involvement of mitogen-activated protein kinases in class B scavenger receptor 
      type I-induced phagocytosis of apoptotic cells.
PG  - 1820-30
AB  - Class B scavenger receptor type I (SR-BI) is a multiligand membrane protein 
      expressed in a variety of cell types. This receptor is responsible for the 
      incorporation of lipids from high density lipoprotein (HDL) by steroidogenic 
      cells, as well as for the phosphatidylserine (PS)-mediated phagocytosis of 
      apoptotic cells by some phagocytic cell types, such as testicular Sertoli cells. 
      Although SR-BI directly binds to PS present on the surface of apoptotic cells, as 
      to whether SR-BI transmits signals to induce engulfment has not been clear. In 
      the present study, we examined this issue using a monoclonal antibody that 
      neutralizes SR-BI activity and a chemical known to be an inhibitor of the 
      SR-BI-mediated incorporation of HDL lipids. The chemical compound inhibited the 
      incorporation of HDL lipids and PS-containing liposomes by an SR-BI-expressing 
      culture cell line, with no effect on the binding of these targets. Similarly, the 
      phagocytosis of PS-exposing apoptotic cells by primary cultured rat Sertoli cells 
      was inhibited in the presence of either reagent, not at the recognition but at 
      the engulfment step. The addition of apoptotic cells or PS-containing liposomes 
      caused a temporal increment of the phosphorylation of all three mitogen-activated 
      protein kinases, p38, extracellular-signal-regulated kinase (ERK) and c-Jun 
      amino-terminal kinase (JNK), in Sertoli cells. The increase of phosphorylated p38 
      and ERK, but not of phosphorylated JNK, was cancelled in the presence of the 
      monoclonal antibody. Furthermore, the level of Sertoli cell phagocytosis of 
      PS-exposing apoptotic cells, as well as that of PS-containing liposomes, was 
      reduced only when the actions of p38 and ERK were simultaneously repressed. In 
      conclusion, these results indicate that SR-BI, when it binds to PS, transmits 
      signals to activate the mitogen-activated protein kinase pathway, which leads to 
      the induction of the engulfment of PS-exposing apoptotic cells by phagocytic 
      cells.
FAU - Osada, Yoichi
AU  - Osada Y
AD  - Graduate School of Medical Science, Kanazawa University, Shizenken, Kakuma-machi, 
      Kanazawa, Ishikawa 920-1192, Japan.
FAU - Shiratsuchi, Akiko
AU  - Shiratsuchi A
FAU - Nakanishi, Yoshinobu
AU  - Nakanishi Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060310
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (Lipids)
RN  - 0 (Liposomes)
RN  - 0 (Phosphatidylserines)
RN  - 0 (Scarb1 protein, rat)
RN  - 0 (Scavenger Receptors, Class B)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Cells, Cultured
MH  - Humans
MH  - Lipids/chemistry
MH  - Liposomes/chemistry/metabolism
MH  - MAP Kinase Signaling System/physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism
MH  - Phagocytosis/*physiology
MH  - Phosphatidylserines/metabolism
MH  - Rats
MH  - Scavenger Receptors, Class B/antagonists & inhibitors/*metabolism
MH  - Sertoli Cells/cytology/physiology
MH  - Testis/cytology
EDAT- 2006/03/15 09:00
MHDA- 2006/08/01 09:00
CRDT- 2006/03/15 09:00
PHST- 2005/11/22 00:00 [received]
PHST- 2006/02/07 00:00 [revised]
PHST- 2006/02/13 00:00 [accepted]
PHST- 2006/03/15 09:00 [pubmed]
PHST- 2006/08/01 09:00 [medline]
PHST- 2006/03/15 09:00 [entrez]
AID - S0014-4827(06)00055-3 [pii]
AID - 10.1016/j.yexcr.2006.02.010 [doi]
PST - ppublish
SO  - Exp Cell Res. 2006 Jun 10;312(10):1820-30. doi: 10.1016/j.yexcr.2006.02.010. Epub 
      2006 Mar 10.