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

Authors


  • Hiroshi Nishiura and Rui Zhao contributed equally to this work.
  • Conflict of Interest: The authors declare that they have no conflict of interest.

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 over-produce 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.

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