Neutrophils in Physiology and Pathology.

Infections, cardiovascular disease, and cancer are major causes of disease and death worldwide. Neutrophils are inescapably associated with each of these health concerns, by either protecting from, instigating, or aggravating their impact on the host. However, each of these disorders has a very different etiology, and understanding how neutrophils contribute to each of them requires understanding the intricacies of this immune cell type, including their immune and nonimmune contributions to physiology and pathology. Here, we review some of these intricacies, from basic concepts in neutrophil biology, such as their production and acquisition of functional diversity, to the variety of mechanisms by which they contribute to preventing or aggravating infections, cardiovascular events, and cancer. We also review poorly explored aspects of how neutrophils promote health by favoring tissue repair and discuss how discoveries about their basic biology inform the development of new therapeutic strategies.

The circadian neutrophil, inside-out.

The circadian clock has sway on a myriad of physiological targets, among which the immune and inflammatory systems are particularly prominent. In this review, we discuss how neutrophils, the wildcard of the immune system, are regulated by circadian oscillations. We describe cell-intrinsic and extrinsic diurnal mechanisms governing the general physiology and function of these cells, from purely immune to homeostatic. Repurposing the concepts discovered in other cell types, we then speculate on various uncharted avenues of neutrophil-circadian relationships, such as topology, metabolism, and the regulation of tissue clocks, with the hope of identifying exciting new avenues of work in the context of circadian immunity.

Reduced Lamin A/C Does Not Facilitate Cancer Cell Transendothelial Migration but Compromises Lung Metastasis.

The mechanisms by which the nuclear lamina of tumor cells influences tumor growth and migration are highly disputed. Lamin A and its variant lamin C are key lamina proteins that control nucleus stiffness and chromatin conformation. Downregulation of lamin A/C in two prototypic metastatic lines, B16F10 melanoma and E0771 breast carcinoma, facilitated cell squeezing through rigid pores, and reduced heterochromatin content. Surprisingly, both lamin A/C knockdown cells grew poorly in 3D spheroids within soft agar, and lamin A/C deficient cells derived from spheroids transcribed lower levels of the growth regulator Yap1. Unexpectedly, the transendothelial migration of both cancer cells in vitro and in vivo, through lung capillaries, was not elevated by lamin A/C knockdown and their metastasis in lungs was even dramatically reduced. Our results are the first indication that reduced lamin A/C content in distinct types of highly metastatic cancer cells does not elevate their transendothelial migration (TEM) capacity and diapedesis through lung vessels but can compromise lung metastasis at a post extravasation level.