Neutrophils and Apoptosis

Fanning, N. F.; Redmond, H. P.; Bouchier-Hayes, D.

doi:10.1142/9781848160774_0006

Cited by 4 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Extended survival could partly explain the pronounced neutrophilia we observed in parturient cows (Fig. 1B), because non-apoptotic neutrophils would not be cleared from circulation (11).…”

Section: Discussionmentioning

confidence: 96%

“…Neutrophils are mature, terminally differentiated leukocytes that normally survive for a short time in the circulation (6-12 h) before undergoing apoptosis and clearance from blood by the body's phagocytic cell network (11). Thus balance between production of new neutrophils in bone marrow and apoptosis in circulating cells largely determines blood neutrophil counts in healthy animals.…”

Section: Discussionmentioning

confidence: 99%

“…The normally short life span of circulating neutrophils is thought to be due to their lack of Bcl-2 gene expression and relatively high level of Fas gene expression (11). Bcl-2 is the prototypic anti-apoptosis protein in most cells that protects mitochondrial membranes from attack by pro-apoptotic Bcl-2 family members such as Bax and Bak (29).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Microarray analysis of gene expression in blood neutrophils of parturient cows

Madsen

Chang

Hickey

et al. 2004

Physiological Genomics

View full text Add to dashboard Cite

It is well documented that blood neutrophils from parturient dairy cows do not perform as well as neutrophils from nonparturient cows in laboratory assays of adhesion, migration, or phagocytosis-induced respiratory burst. However, little is known about the possible molecular basis for parturition-induced changes in neutrophils. cDNA microarray analysis was used in the current study to explore parturition-induced changes in gene expression profiles in bovine blood neutrophils. Total RNA from isolated blood neutrophils of four parturient Holstein cows was obtained before, during, and after parturition, reverse transcribed into cDNA, and sequentially labeled with Cy3 or Cy5 dyes prior to paired hybridizations to 1,056 member bovine total leukocyte (BOTL-3) microarrays in a loop design. Resulting gene expression data were LOWESS normalized by array and analyzed using a mixed model approach. Results showed that expression profiles for 302 BOTL-3 genes were influenced by parturition. BLASTn analysis and preliminary clustering of affected genes by biological function indicated that the largest proportion (14%) of changed genes encode proteins critical to regulation of apoptosis. Independent confirmation of altered expression for 16 of these genes was achieved using quantitative real-time RT-PCR (Q-RT-PCR). A predominantly survival phenotype inferred from the microarray and Q-RT-PCR results was substantiated by monitoring apoptosis status of blood neutrophils from castrated male cattle cultured in the presence of sera from parturient cows. Thus our combined gene expression and apoptosis phenotyping results suggest that bovine parturition may induce prolonged survival in normally short-lived blood neutrophils.

show abstract

“…Extended survival could partly explain the pronounced neutrophilia we observed in parturient cows (Fig. 1B), because non-apoptotic neutrophils would not be cleared from circulation (11).…”

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Microarray analysis of gene expression in blood neutrophils of parturient cows

Madsen

Chang

Hickey

et al. 2004

Physiological Genomics

View full text Add to dashboard Cite

show abstract

“…Neutrophil apoptosis occurs through two main pathways (reviewed by Fanning et al 1999), one that is mediated via exogenous death receptor signaling (Liles et al 1996) and the other that occurs spontaneously through mitochondrial membrane changes under the influence of Bcl-2 family proteins (Lin et al 1996). In the current study, we chose to examine the main exogenous death receptor of neutrophils, Fas.…”

Section: Introductionmentioning

confidence: 99%

Effects of glucocorticoids on Fas gene expression in bovine blood neutrophils

Chang

Madsen

Toelboell

et al. 2004

Journal of Endocrinology

View full text Add to dashboard Cite

Blood neutrophils are extremely short-lived cells that are programmed for rapid apoptosis after differentiation in bone marrow. Recently, glucocorticoids have been shown to prolong survival of human and rodent neutrophils, but the mechanisms and implications for leukocyte homeostasis and health are unclear. In this study, we investigated the effects of endogenous and exogenous glucocorticoids on Fas expression in bovine neutrophils because Fas is a major death receptor that stimulates apoptosis in circulating cells. Our study subjects were four periparturient dairy cows whose blood concentrations of cortisol peaked at calving, 15 dexamethasone-treated steers and three untreated steers whose neutrophils were exposed to dexamethasone in vitro. Fas mRNA abundance changes in collected neutrophils were monitored numerous times relative to the in vivo glucocorticoid challenges, and the relationships between these data and circulating neutrophil counts were estimated by correlation analyses. Fas mRNA and protein abundance, caspase 8 activity, and survival of neutrophils in vitro were also monitored in the presence and absence of dexamethasone. In the periparturient cows, Fas mRNA abundance in circulating neutrophils showed a sharp decrease between calving and 12 h postpartum. Based on PROC CORR analysis (SAS), this correlated negatively with blood neutrophil count (r=-0.634; P=0.0009) and serum cortisol concentration (r=-0.659; P<0.0001), but showed no relationship with serum progesterone or estradiol concentrations (P > or =0.09). Administration of dexamethasone to steers also caused a pronounced reduction in neutrophil Fas mRNA abundance that persisted for 12 h and correlated negatively with blood neutrophil count (r=-0.748; P=0.0021). In vitro, dexamethasone caused dose-dependent loss of GR proteins from the cytosol of neutrophils concurrently with Fas mRNA downregulation, which was inhibited by the glucocorticoid receptor (GR) antagonist, RU486. Dexamethasone treatment of cultured neutrophils also reduced surface Fas expression, spontaneous and sFasL-induced caspase 8 activity, and rate of apoptosis in the cells. Taken together, these in vivo and in vitro results suggest that glucocorticoids inhibit Fas expression in bovine blood neutrophils via GR activation, possibly contributing to the cells' increased longevity in culture and the pronounced neutrophilia observed in parturient cows and hormone-treated steers. We thus conclude that glucocorticoid-activated GR may change the homeostasis of circulating neutrophils, in part through its negative effects on Fas gene expression and downstream apoptosis signaling pathways.

show abstract

“…This incubation period in vitro was chosen because Lamas & Ellis [23] demonstrated a decrease in the viability of unstimulated Atlantic salmon neutrophils after 4 days. In mammals it has been shown that the life span of neutrophils is mainly regulated by soluble factors being present in inflammatory milieus [24]. We therefore suggest that the contact of HKL with T. borreli induces apoptosis-preventing signals for carp neutrophils.…”

Section: Discussionmentioning

confidence: 69%