TITLE:
New aspects of the C5a receptor
AUTHORS:
Hiroshi Nishiura, Kiyoshi Ohura
KEYWORDS:
Adhesion; Apoptosis; C5a Receptor; Differentiation; G Protein-Coupled Receptor; Neutrophils; Periodontitis; Ribosomal Protein S19
JOURNAL NAME:
Advances in Bioscience and Biotechnology,
Vol.5 No.1,
January
15,
2014
ABSTRACT: The process of apoptotic cell death for maintenance
of cell homeostasis is now believed to be flexible. To examine the mechanism for
this flexibility, the process of programmed cell death is sometimes divided
into three phases: initiation, effector and execution. We have demonstrated
that apoptotic cells commonly express a de
novo synthesized C5a receptor (C5aR), which
belongs to the G protein-coupled receptor (GPCR) family. A natural
agnostic ligand of the C5aR, C5a, is produced from plasma C5 by C5 convertase
in the early phase of acute inflammation. Although it is not realistic, we
found that C5a can adjust apoptotic cell lifespan long. We recently have read
interesting reports that apoptotic cells can release natural agnostic ligands at
the initiation phase and corresponding GPCRs are already expressed on cell
surfaces of apoptotic cells. Conversely, we found that apoptotic cells commonly
release an alternative antagonistic/agnostic ligand of the de novo synthesized C5aR, ribosomal protein S19 (RP S19) polymer.
The RP S19 polymer can adjust apoptotic cell lifespan short. Importantly, the
C5a-dependent regulation is limited by the C5aR sensitization, but the RP S19
polymer-dependent regulation is unlimited by the C5aR desensitization. Therefore,
we suggested that apoptotic cells commonly release agnostic ligands in the
initiation phase that should lengthen intermittently a period of the initiation
phase. Next, apoptotic cells commonly release antagonistic/agnostic ligands in the
effector phase that should continue shortening a period of the effector phase.
In addition, we know that an inherited erythroblastopenia is associated with
mutations in the RP S19 gene. However,
the roles of RP S19 in the formation of erythroblast-macrophage islands are
not clearly understood. We recently have found that a different arm that the RP
S19 polymer has connects the de novo synthesized C5aR on erythroblasts and the
generally expressed C5aR on macrophages. Therefore, we suggested that apoptotic
cells commonly release antagonistic/agnostic ligands in the execution phase
that should continue connecting apoptotic cells and macrophages in the execution
phase for shortening a period of the execution phase. In this review, we introduce
new aspects of the C5aR in apoptotic cells and discuss the effects of the long
lifespan of apoptotic cell-like neutrophils on the development of periodontitis.