Women are conferred with greater immunologic and survival benefits compared to men. Female sex steroids contribute to this sexual dimorphism. Furthermore, during human pregnancy when female sex hormones are elevated, neutrophil apoptosis is delayed. This study examines the specific effects of estradiol and progesterone on neutrophil apoptosis and function in healthy adult men and women. We also examined the contribution of these hormones to the persistence and resolution of an inflammatory response. Spontaneous apoptosis was significantly decreased in women compared with men. Physiologic doses of estradiol and progesterone caused a further delay in spontaneous apoptosis in both men and women but did not diminish Fas antibodyinduced apoptosis. The delay in apoptosis was mediated at the level of the mitochondria with decreased release of cytochrome c, which may alter caspase cleavage and activity. There were no associated alterations in neutrophil CD11b, but production of reactive oxygen intermediates (ROIs) in women was increased. Thus, female sex hormones mediate delayed neutrophil apoptosis in both sexes and enhance female intracellular production of ROIs. Modulating hormonal responses may be an effective therapeutic tool in combating inflammatory diseases. IntroductionFrom conception to senescence, women have a significant survival advantage. 1 Men are more susceptible to sepsis and subsequent morbidity and mortality than women of reproductive age. [2][3][4] The incidence of sepsis in postmenopausal women increases to levels almost equal to those seen in age-matched men. 5,6 The exact mechanism mediating this sexual dimorphism is unclear. However, female sex hormones have been implicated because they modulate the immune system under normal and stress conditions. 7 Following trauma or hemorrhage, female mice maintain their immune function, whereas male mice have significantly depressed responses. 8 Estradiol has been shown to be protective in organ ischemia-reperfusion injury and shock by preventing androgeninduced immunosuppression in male animals. 9-12 Thus, female sex hormones may be a useful adjunct in preventing trauma-induced immunosuppression and the associated increased susceptibility to sepsis. 13 Estrogen treatment, testosterone depletion, and testosterone receptor antagonists improve outcome in male animals following trauma and sepsis. 14 The exact role of changes in the estradiol-testosterone ratio in immune function requires further clarification. Estrogens are also cited as having a protective role in neurodegenerative and cardiac diseases through a variety of mechanisms including blockade of oxidation, antagonism of nitric oxide synthase activity, 15 and interference with the apoptotic process in a variety of cell systems.Altered neutrophil apoptosis has been implicated in the pathogenesis of several inflammatory conditions. 16,17 Excessively delayed neutrophil apoptosis is associated with the systemic inflammatory response syndrome (SIRS). This syndrome is also characterized by activated neutro...
It seems to me that anyone who has ever flicked through copies of the UK's practitioner magazine Planning cannot fail to recognize some of the problems referenced by Luuk Boelens in his call for an actor-relational approach (ARA). The pages of Planning document seemingly perpetual calls for planners to synchronize their visions and schemes with the latest turn in government policy or with the minutiae of new environmental legislation or some new (and probably economistic) direction to measure this and consider that.Meanwhile, entrenched professional attitudes and risk averse local authority practices are just some of the problems planners face as they try to broker the support of the constellation of partners they need on board if they are to stand a chance of creating a deliverable vision. Wouldn't it be nice if a new discourse of associative democracy could free up at least some of our planners to engage in more generative work, seeking immanent possibilities by reconnecting local actors in creative new ways? There is undoubtedly a need for the kind of theory Luuk Boelens is seeking to create. What is more, by the look of the case studies, it seems to work.But before we are carried off in our enthusiasm for an 'outside-inward' brand of creative planning, there is a need for some critical scrutiny of how a 'trans-modern' ARA might affect the way we handle spatial development deficits and controversies. The ARA references actor-network theory as part of a body of theoretical support for its premises. It seems fitting, therefore, to consider the ARA in the same way that science and technology studies scholars would consider the design and implementation of a new technology. Actor-network theory scholars see such technologies as political movements comprised of hybrid assemblages of human and non-human actors. Consequently, Sheila Jasanoff (2003) suggests four questions which are appropriate in instances where the impact of a technology is uncertain. She asks: what is at issue? Who will be hurt? Who benefits? How can we know? This comment piece develops these
SummaryThe diagnosis of neonatal sepsis is difficult, resulting in unnecessary treatment to minimize morbidity and mortality. We hypothesized that exposure to antenatal risk factors for sepsis alters the perinatal neutrophil phenotype. The study setting was a tertiary referral university-affiliated maternity and neonatal hospital. Neutrophils from adults, normal neonates, neonates with antenatal sepsis risk factors and their respective maternal samples were incubated alone, with agonistic Fas antibody or with lipopolysaccharide (LPS). Surface receptor CD11b expression and the percentage apoptosis (persistent inflammatory response) were assessed using flow cytometry. Both mothers and asymptomatic neonates exposed to maternal sepsis risk factors had increased spontaneous neutrophil apoptosis compared to their respective controls. Infants with sepsis were LPS and Fas hyporesponsive. Maternal neutrophils had a delay in apoptosis in all groups with enhanced LPS and Fas responses associated with neonatal sepsis. CD11b expression was not altered significantly between groups. Maternal neutrophil function is altered in neonatal sepsis and may have a diagnostic role. Neonatal sepsis was associated with LPS hyporesponsiveness, potentially increasing susceptibility to infection.
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