Inducible cyclooxygenase-derived 15-deoxy(Delta)12-14PGJ2 brings about acute inflammatory resolution in rat pleurisy by inducing neutrophil and macrophage apoptosis.
Failure of acute inflammation to resolve leads to persistence of the inflammatory response and may contribute to the development of chronic inflammation. Thus, an understanding of inflammatory resolution will provide insight into the etiology of chronic inflammation. In an acute pleurisy, polymorphonuclear leukocytes (PMNs) were found to predominate at the onset of the lesion but decreased in number by undergoing apoptosis, the principal mechanism by which PMNs died in this model. PMNs were progressively replaced by monocytes, which differentiated into macrophages. As with PMNs, macrophages also underwent programmed cell death leading to an abatement of the inflammatory response and eventual resolution. It was found that apoptosis of both these inflammatory cell types was mediated by pro-resolving cyclooxygenase 2-derived 15deoxyDelta12-14PGJ2, which is uniquely expressed during active resolution. Although PMN programmed cell death is well understood, the observation that macrophages apoptose during resolution of acute inflammation is less well described. These results provide insight into the mechanisms that switch off acute inflammation and prevent complications of wound healing and potentially the development of immune-mediated chronic inflammation.
Gilroy
Derek W
DW
Department of Experimental Pathology, William Harvey Research Institute, St. Bartholomew's & The Royal London School of Medicine and Dentistry, London EC1M 6BQ, UK. d.w.gilroy@qmul.ac.uk
Colville-Nash
Paul R
PR
McMaster
Shaun
S
Sawatzky
Deborah A
DA
Willoughby
Derek A
DA
Lawrence
Toby
T
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D051546:Cyclooxygenase 2; D007249:Inflammation / Q000201:enzymology; D007527:Isoenzymes / Q000378:metabolism / Q000502:physiology*; D007958:Leukocyte Count; D008264:Macrophages / Q000276:immunology*; D018448:Models, Immunological; D009504:Neutrophils / Q000276:immunology*; D010998:Pleurisy / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000096:biosynthesis; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism / Q000502:physiology*; D051381:Rats
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D007527:Isoenzymes; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015230:Prostaglandin D2