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Programmed cell clearance: From nematodes to humans.

ABSTRACT: Programmed cell clearance is a highly regulated physiological process of elimination of dying cells that occurs rapidly and efficiently in healthy organisms. It thus ensures proper development as well as homeostasis. Recent studies have disclosed a considerable degree of conservation of cell clearance pathways between nematodes and higher organisms. The externalization of the anionic phospholipid phosphatidylserine (PS) has emerged as an important "eat-me" signal for phagocytes and its exposition on apoptotic cells is controlled by phospholipid translocases and scramblases. However, there is mounting evidence that PS exposure occurs not only in apoptosis, but may also be actively expressed on the surface of cells undergoing other forms of cell death including necrosis; PS is also expressed on the surface of engulfing cells. Additionally, PS may act as a "save-me" signal during axonal regeneration. Here we discuss mechanisms of PS exposure and its recognition by phagocytes as well as the consequences of PS signaling in nematodes and in mammals.

SUBMITTER: Kloditz K

PROVIDER: S-EPMC5476906 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Programmed cell clearance: From nematodes to humans.

Klöditz Katharina K Chen Yu-Zen YZ Xue Ding D Fadeel Bengt B

Biochemical and biophysical research communications 20161202 3

Programmed cell clearance is a highly regulated physiological process of elimination of dying cells that occurs rapidly and efficiently in healthy organisms. It thus ensures proper development as well as homeostasis. Recent studies have disclosed a considerable degree of conservation of cell clearance pathways between nematodes and higher organisms. The externalization of the anionic phospholipid phosphatidylserine (PS) has emerged as an important "eat-me" signal for phagocytes and its expositio ...[more]

PMID: 27919685

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Project description:BACKGROUND: Successful embryogenesis is a critical rate limiting step for the survival and transmission of parasitic worms as well as pathology mediated by them. Hence, blockage of this important process through therapeutic induction of apoptosis in their embryonic stages offers promise for developing effective anti-parasitic measures against these extra cellular parasites. However, unlike in the case of protozoan parasites, induction of apoptosis as a therapeutic approach is yet to be explored against metazoan helminth parasites. METHODOLOGY/PRINCIPAL FINDINGS: For the first time, here we developed and evaluated flow cytometry based assays to assess several conserved features of apoptosis in developing embryos of a pathogenic filarial nematode Setaria digitata, in-vitro as well as ex-vivo. We validated programmed cell death in developing embryos by using immuno-fluorescence microscopy and scoring expression profile of nematode specific proteins related to apoptosis [e.g. CED-3, CED-4 and CED-9]. Mechanistically, apoptotic death of embryonic stages was found to be a caspase dependent phenomenon mediated primarily through induction of intracellular ROS. The apoptogenicity of some pharmacological compounds viz. DEC, Chloroquine, Primaquine and Curcumin were also evaluated. Curcumin was found to be the most effective pharmacological agent followed by Primaquine while Chloroquine displayed minimal effect and DEC had no demonstrable effect. Further, demonstration of induction of apoptosis in embryonic stages by lipid peroxidation products [molecules commonly associated with inflammatory responses in filarial disease] and demonstration of in-situ apoptosis of developing embryos in adult parasites in a natural bovine model of filariasis have offered a framework to understand anti-fecundity host immunity operational against parasitic helminths. CONCLUSIONS/SIGNIFICANCE: Our observations have revealed for the first time, that induction of apoptosis in developing embryos can be a potential approach for therapeutic intervention against pathogenic nematodes and flow cytometry can be used to address different issues of biological importance during embryogenesis of parasitic worms.

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Programmed cell clearance: From nematodes to humans.

Publications

Programmed cell clearance: From nematodes to humans.

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