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Fas-mediated neutrophil apoptosis and associated A1 protein expression during systemic inflammation are regulated independently of both tumor necrosis factor receptors.
Shock. 2003 Mar; 19(3):201-7.S

Abstract

TNFR-1 (p55) and Fas share a death domain which is critical for apoptosis signaling whereas TNFR-p55 and TNFR-2 (p75) can activate NF-kappaB leading to anti-apoptotic proteins expression such as A1. The purpose of this study was to elucidate the role(s) of TNFR-p55 and TNFR-p75 in Fas-mediated neutrophil apoptosis and A1 expression in a mouse model of endotoxemia. Gene knockout (KO) (p55-/-, p75-/-, p55(-/-)/p75(-/-)) or wild type (WT) mice were injected i.p. with saline or LPS (4 microg/g) followed by collecting peripheral blood after 24 h. Neutrophil apoptosis was assessed by propidium iodide staining using two-color flow cytometry with granulocyte-specific Gr1-FITC after 6-h whole blood culture with or without Fas agonist Jo2 (300 ng/ml) in the presence or absence of cycloheximide (CHX, 30 microg/ml). Membrane-associated receptors (Fas, TNFR-p55 and TNFR-p75) and cytoplasmic A1 expression of freshly isolated neutrophils were assessed by one-color flow cytometry and western blotting respectively. Compared with the group-WT/Sal, Jo2 induced apoptosis only in the presence of CHX (J+C). J+C-induced apoptosis was significantly lower in the group-p55(-/-)/Sal and p55(-/-)/p75(-/-)/Sal but not in the group-p75(-/-)/Sal. J+C-induced apoptosis was inhibited similarly in all the LPS-injected WT and KO mice. Strong A1 expression was also induced similarly in all the LPS-injected WT and KO mice. Fas and TNFR-p55 expression was normal and TNFR-p75 was significantly increased in all the LPS-injected WT and KO mice although absence of the appropriate surface receptors was confirmed in the KO mice. We conclude that p55 normally plays a proapoptotic role, but p75 appears to play a minimal role in Fas-mediated neutrophil apoptosis. During endotoxin-induced systemic inflammation, both TNFR-p55 and TNFR-p75 appear to be of minimal importance for modulation of Fas-mediated apoptosis and associated A1 protein expression despite normal Fas/TNFR-p55 and increased TNFR-p75 expression in neutrophils.

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Authors+Show Affiliations

Kotani J
Department of Surgery, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903,USA.
Avallone NJ
No affiliation info available
Lin E
No affiliation info available
Goshima M
No affiliation info available
Gandhi K
No affiliation info available
Lowry SF
No affiliation info available
Calvano SE
No affiliation info available

MeSH

AnimalsAntigens, CDApoptosisBiomarkersBone Marrow CellsDNA-Binding ProteinsGene Expression RegulationGenes, bcl-2InflammationLipopolysaccharidesMiceMice, KnockoutNeutrophilsReceptors, Tumor Necrosis FactorReceptors, Tumor Necrosis Factor, Type IReceptors, Tumor Necrosis Factor, Type IIReplication Protein Cfas Receptor

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12630518

Citation

Kotani, Joji, et al. "Fas-mediated Neutrophil Apoptosis and Associated A1 Protein Expression During Systemic Inflammation Are Regulated Independently of Both Tumor Necrosis Factor Receptors." Shock (Augusta, Ga.), vol. 19, no. 3, 2003, pp. 201-7.
Kotani J, Avallone NJ, Lin E, et al. Fas-mediated neutrophil apoptosis and associated A1 protein expression during systemic inflammation are regulated independently of both tumor necrosis factor receptors. Shock. 2003;19(3):201-7.
Kotani, J., Avallone, N. J., Lin, E., Goshima, M., Gandhi, K., Lowry, S. F., & Calvano, S. E. (2003). Fas-mediated neutrophil apoptosis and associated A1 protein expression during systemic inflammation are regulated independently of both tumor necrosis factor receptors. Shock (Augusta, Ga.), 19(3), 201-7.
Kotani J, et al. Fas-mediated Neutrophil Apoptosis and Associated A1 Protein Expression During Systemic Inflammation Are Regulated Independently of Both Tumor Necrosis Factor Receptors. Shock. 2003;19(3):201-7. PubMed PMID: 12630518.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fas-mediated neutrophil apoptosis and associated A1 protein expression during systemic inflammation are regulated independently of both tumor necrosis factor receptors. AU - Kotani,Joji, AU - Avallone,Nicholas J, AU - Lin,Edward, AU - Goshima,Masahiro, AU - Gandhi,Kishor, AU - Lowry,Stephen F, AU - Calvano,Steve E, PY - 2003/3/13/pubmed PY - 2003/10/16/medline PY - 2003/3/13/entrez SP - 201 EP - 7 JF - Shock (Augusta, Ga.) JO - Shock VL - 19 IS - 3 N2 - TNFR-1 (p55) and Fas share a death domain which is critical for apoptosis signaling whereas TNFR-p55 and TNFR-2 (p75) can activate NF-kappaB leading to anti-apoptotic proteins expression such as A1. The purpose of this study was to elucidate the role(s) of TNFR-p55 and TNFR-p75 in Fas-mediated neutrophil apoptosis and A1 expression in a mouse model of endotoxemia. Gene knockout (KO) (p55-/-, p75-/-, p55(-/-)/p75(-/-)) or wild type (WT) mice were injected i.p. with saline or LPS (4 microg/g) followed by collecting peripheral blood after 24 h. Neutrophil apoptosis was assessed by propidium iodide staining using two-color flow cytometry with granulocyte-specific Gr1-FITC after 6-h whole blood culture with or without Fas agonist Jo2 (300 ng/ml) in the presence or absence of cycloheximide (CHX, 30 microg/ml). Membrane-associated receptors (Fas, TNFR-p55 and TNFR-p75) and cytoplasmic A1 expression of freshly isolated neutrophils were assessed by one-color flow cytometry and western blotting respectively. Compared with the group-WT/Sal, Jo2 induced apoptosis only in the presence of CHX (J+C). J+C-induced apoptosis was significantly lower in the group-p55(-/-)/Sal and p55(-/-)/p75(-/-)/Sal but not in the group-p75(-/-)/Sal. J+C-induced apoptosis was inhibited similarly in all the LPS-injected WT and KO mice. Strong A1 expression was also induced similarly in all the LPS-injected WT and KO mice. Fas and TNFR-p55 expression was normal and TNFR-p75 was significantly increased in all the LPS-injected WT and KO mice although absence of the appropriate surface receptors was confirmed in the KO mice. We conclude that p55 normally plays a proapoptotic role, but p75 appears to play a minimal role in Fas-mediated neutrophil apoptosis. During endotoxin-induced systemic inflammation, both TNFR-p55 and TNFR-p75 appear to be of minimal importance for modulation of Fas-mediated apoptosis and associated A1 protein expression despite normal Fas/TNFR-p55 and increased TNFR-p75 expression in neutrophils. SN - 1073-2322 UR - https://www.unboundmedicine.com/medline/citation/12630518/Fas_mediated_neutrophil_apoptosis_and_associated_A1_protein_expression_during_systemic_inflammation_are_regulated_independently_of_both_tumor_necrosis_factor_receptors_ L2 - https://doi.org/10.1097/00024382-200303000-00002 DB - PRIME DP - Unbound Medicine ER -