isolation-of-human-neutrophils-from-whole-blood-and-buffy-coats

Isolation of Human Neutrophils from Whole Blood and Buffy Coats

Neutrophils (PMNs) are the most abundant leukocytes in human circulation, ranging from 40 to 70% of total blood leukocytes. They are the first cells ...

neutrophil-lifespan-extension-with-clon-g-an-vitro-spontaneous-death

Neutrophil Lifespan Extension with CLON-G and an <em>In Vitro</em> Spontaneous Death Assay

The average lifespan of a neutrophil is less than 24 h, which limits basic research on neutrophils and the application of neutrophil studies. Our previous ...

Harvard Medical School, Department of Lab Medicine, Children’s Hospital Boston, and Dana-Farber/Harvard Cancer Center

Dana-Farber /Harvard Cancer Center

The Golgi apparatus (GA) is the hub of intracellular trafficking, but selectively targeting GA remains a challenge. We show an unconventional types of peptide thioesters, consisting of an aminoethyl thioester and acting as substrates of thioesterases, for instantly targeting the GA of cells. The peptide thioesters, above or below their critical micelle concentrations, enter cells mainly via caveolin-mediated endocytosis or macropinocytosis, respectively. After being hydrolyzed by GA-associated thioesterases, the resulting thiopeptides form dimers and accumulate in the GA. After saturating the GA, the thiopeptides are enriched in the endoplasmic reticulum (ER). Their buildup in ER and GA disrupts protein trafficking, thus leading to cell death via multiple pathways. The peptide thioesters target the GA of a wide variety of cells, including human, murine, and  cells. Changing d-diphenylalanine to l-diphenylalanine in the peptide maintains the GA-targeting ability. In addition, targeting GA redirects protein (e.g., NRAS) distribution. This work illustrates a thioesterase-responsive and redox-active molecular platform for targeting the GA and controlling cell fates.

Enzyme-Responsive Peptide Thioesters for Targeting Golgi Apparatus.

Neutrophil-specific depletion of gasdermin D does not protect against murine sepsis.

Neutrophils play an essential role in the defense against bacterial infections and orchestrate both the innate and adaptive immune responses. With their abundant numbers, diverse function and short life span, these cells are at the forefront of immune responses, and have gained attention in recent years because of their presence in tumor sites. Neutrophil involvement pertains to tumor cells' ability to construct a suitable tumor microenvironment (TME) that accelerates their own growth and malignancy, by facilitating their interaction with surrounding cells through the circulatory and lymphatic systems, thereby influencing tumor development and progression. Studies have indicated both pro- and anti-tumor properties of infiltrating neutrophils. The TME can exploit neutrophil function, recruitment, and even production, thus resulting in pro-tumor properties of neutrophils, including promotion of genetic instability, tumor cell proliferation, angiogenesis and suppression of anti-tumor or inflammatory response. In contrast, neutrophils can mediate anti-tumor resistance by direct cytotoxicity to the tumor cells or by facilitating anti-tumor functions  crosstalk with T cells. Here, we summarize current knowledge regarding the effects of neutrophil heterogeneity under homeostatic and tumor conditions, including neutrophil phenotype and function, in cancer biology.

ArticleTotal : 2	Year
Publication title Cited by 11	2021
Publication title Cited by 5	2023

Article	Year
Enzyme-Responsive Peptide Thioesters for Targeting Golgi Apparatus. Journal of the American Chemical Society\| PubMed ID: 35404599	2022
Neutrophil-specific depletion of gasdermin D does not protect against murine sepsis. Blood\| PubMed ID: 36332166	2023
Heterogeneity of neutrophils in cancer: one size does not fit all. Cancer biology & medicine\| PubMed ID: 36514901	2022

Alan Y. Hsu

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