Involvement of regional neutrophil apoptosis promotion by ribosomal protein S19 oligomers in resolution of experimental acute inflammation

Abstract

Isolated peripheral neutrophils spontaneously underwent apoptosis in association with extra-cellular liberation of the monocyte-attracting ribosomal protein S19 (RP S19) oligomers. This apoptosis was prevented by the simultaneous presence of anti-RP S19 antibodies or of a C5a receptor antagonist, but was promoted by supplementing extrinsic RP S19 oligomers. Transformed HL-60 cells to overproduce Gln137Asn-mutant RP S19 were differentiated to neutrophil-like cells. The neutrophil-like cells gained resistance against the spontaneous apoptosis concomitant with the generation of non-functional RP S19 oligomers. When the neutrophil-like cells were intradermally transplanted into mice, the mutant RP S19-producing neutrophils persisted for a long period of time, whereas wild-type RP S19-producing neutrophils underwent apoptosis and were promptly cleared by infiltrated macrophages. When an experimental pleurisy was introduced by injecting carrageenan into the pleural cavity of mice, the inflammation spread slightly to lung parenchyma. When antibodies neutralizing the RP S19 oligomers were simultaneously administrated with carrageenan, the neutrophil infiltration in the lung parenchymal lesion become more severe, occurring as alveolar septal destruction and hemorrhage concomitant with an augmented neutrophil number in the pleural exudate. These results indicate the importance of the RP S19 oligomers and the C5a receptor in neutrophil clearance and acute inflammation resolution.

The effect of ribosomal protein S15a in lung adenocarcinoma

“…So far, most ribosomal proteins have been identified to bind to certain regions of ribosomal RNA and perform catalytic functions. Many ribosomal proteins have various extra-ribosomal functions, such as DNA repair, transformation, development, apoptosis, and transcription ( Lee et al, 2010 ; Nishiura et al, 2013 ; Nosrati, Kapoor & Kumar, 2014 ). Some studies show that these proteins may play a role in human tumor development and progression.…”

The roles of ribosomal protein S19 C-terminus in a shortened neutrophil lifespan through delta lactoferrin

“…The RP S19 polymer does not induce a C5aR-mediated downstream signal but stimulates RGS3 expression via the C5aR on neutrophils (Nishiura et al, , 2009(Nishiura et al, , 2010a. Therefore, we suggested that RGS3 expression via de novo-synthesized C5aR on neutrophils participates in the shortening of the cell lifespan (Nishiura, 2013;Nishiura et al, 2013).…”

Effects of ghrelin on the apoptosis of human neutrophils in vitro

“…Neutrophils, the most numerous immune cells in the first line of protection against invading microbes, are characterized by a very short lifespan ( 27 ); their normally short lifespan in the circulation can be manipulated and extended at sites of inflammation, to ensure that an appropriate host response is mounted in response to infection or tissue injury. However, uncontrolled neutrophil recruitment or inappropriate neutrophil longevity is pathophysiologically involved in the development of inflammatory diseases with unresolved neutrophilic inflammation ( 28 ). For instance, a delay in apoptosis may lead to the prolonged release of neutrophil products and direct tissue injury, thus participating in the development of ARDS ( 10 ).…”