Roles of the ribosomal protein S19 dimer and the C5a receptor in pathophysiological functions of phagocytic leukocytes.
Monocytes and neutrophils, the major phagocytic leukocytes, migrate to inflammatory sites by sensing chemoattractants such as anaphylatoxin C5a with membrane receptors such as C5a receptor. Upon stimulation, the leukocytes increase cytoplasmic Ca(2+) concentration and generate radical oxygen species. These leukocytes have different functions in inflammation. Neutrophils migrate more rapidly and induce vascular plasma leakage upon infiltration. Monocytes infiltrate tissue more slowly but have superior capacities of phagocytosis and antigen presentation. There must be mechanisms to separately recruit the leukocyte species at an inflammatory site. Ribosomal protein S19 (RP S19) is a component of ribosome. During apoptosis, RP S19 is dimerized and obtains a ligand capacity to C5a receptor. The RP S19 dimer attracts monocytes to phagocytically clear the apoptotic cells that released the dimer molecules. The phagocytic monocytes/macrophages then translocate to regional lymph nodes and present apoptotic cell-derived antigens. Oppositely, the RP S19 dimer inhibits C5a-induced neutrophil migration and promotes apoptosis of neutrophils via the C5a receptor. The RP S19 dimer seems to prevent excessive tissue destruction induced by neutrophils. Skp is a molecular chaperon of Gram-negative bacteria. Skp also attracts monocytes and neutrophils as a ligand of C5a receptor. However, it promotes neither cytoplasmic Ca(2+) enhancement nor radical oxygen generation.
Yamamoto
Tetsuro
T
Department of Molecular Pathology, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University Graduate School, Honjo, Kumamoto, Japan. tetsu@gpo.kumamoto-u.ac.jp
D017209:Apoptosis / Q000502:physiology; D002630:Chemotactic Factors / Q000502:physiology; D006801:Humans; D009000:Monocytes / Q000473:pathology / Q000502:physiology*; D009504:Neutrophils / Q000473:pathology / Q000502:physiology*; D010587:Phagocytosis / Q000502:physiology; D044087:Receptor, Anaphylatoxin C5a / Q000502:physiology*; D012269:Ribosomal Proteins / Q000502:physiology*
D002630:Chemotactic Factors; D044087:Receptor, Anaphylatoxin C5a; D012269:Ribosomal Proteins; C040343:ribosomal protein S19