Neutrophils in cancer: neutral no more

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

STAT5 Is an Ambivalent Regulator of Neutrophil Homeostasis

BACKGROUND: Although STAT5 promotes survival of hematopoietic progenitors, STAT5-/- mice develop mild neutrophilia. METHODOLOGY/PRINCIPAL FINDINGS: Here, we show that in STAT5-/- mice, liver endothelial cells (LECs) autonomously secrete high amounts of G-CSF, allowing myeloid progenitors to overcompensate for their intrinsic survival defect. However, when injected with pro-inflammatory cytokines, mutant mice cannot further increase neutrophil production, display a severe deficiency in peripheral neutrophil survival, and are therefore unable to maintain neutrophil homeostasis. In wild-type mice, inflammatory stimulation induces rapid STAT5 degradation in LECs, G-CSF production by LECs and other cell types, and then sustained mobilization and expansion of long-lived neutrophils. CONCLUSION: We conclude that STAT5 is an ambivalent factor. In cells of the granulocytic lineage, it exerts an antiapoptotic function that is required for maintenance of neutrophil homeostasis, especially during the inflammatory response. In LECs, STAT5 negatively regulates granulopoiesis by directly or indirectly repressing G-CSF expression. Removal of this STAT5-imposed brake contributes to induction of emergency granulopoiesis.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Dynamic purine signaling and metabolism during neutrophil–endothelial interactions

During episodes of hypoxia and inflammation, polymorphonuclear leukocytes (PMN) move into underlying tissues by initially passing between endothelial cells that line the inner surface of blood vessels (transendothelial migration, TEM). TEM creates the potential for disturbances in vascular barrier and concomitant loss of extravascular fluid and resultant edema. Recent studies have demonstrated a crucial role for nucleotide metabolism and nucleoside signaling during inflammation. These studies have implicated multiple adenine nucleotides as endogenous tissue protective mechanisms invivo. Here, we review the functional components of vascular barrier, identify strategies for increasing nucleotide generation and nucleoside signaling, and discuss potential therapeutic targets to regulate the vascular barrier during inflammation

O ambiente educacional do curso de Graduação em Enfermagem na perspectiva dos estudantes

RESUMO Objetivo Avaliar o ambiente educacional da Escola de Enfermagem da Universidade de São Paulo, na perspectiva do estudante. Método Abordagem quantitativa com desenho exploratório. Participaram do estudo, 176 estudantes que responderam a uma escala Likert, com graduação de 1 a 5 para avaliação do ambiente educacional. Os dados foram submetidos à análise fatorial exploratóriae testes estatísticos inferenciais; a confiabilidade do instrumento foi constatada pelo Alpha de Cronbach. Resultados A análise de dimensionalidade estabeleceu quatro fatores: Suporte à aprendizagem prática, com média de escore 3,64; Atitudes durante a aprendizagem, escore médio 2,92; Clima de aprendizagem, média 3,58 e Fragilidades da aprendizagem com 3,04. Conclusão O fator mais favorável do ambiente foi o Suporte à aprendizagem. As competências atitudinais atingiram escores mais baixos, sugerindo a necessidade de fortalecer esses aspectos durante a graduação