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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.

Authors+Show Affiliations

Department of Surgery, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903,USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

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 -