Differences between human male and female neutrophils in mRNA, translation efficiency, protein, and phosphoprotein profiles.

Background: Human males and females show differences in the incidence of neutrophil-associated diseases such as systemic lupus erythematosus, rheumatoid arthritis, and reactive arthritis, and differences in neutrophil physiological responses such as a faster response to the chemorepellent SLIGKV. Little is known about the basis of sex-based differences in human neutrophils.

Methods: Starting with human neutrophils from healthy donors, we used RNA-seq to examine total mRNA profiles, mRNAs not associated with ribosomes and thus not being translated, mRNAs in monosomes, and mRNAs in polysomes and thus heavily translated.

A phosphatidylinositol phosphate kinase inhibits Ras activation and regulates chemorepulsion in Dictyostelium discoideum.

During developmental and immune responses, cells move towards or away from some signals. Although much is known about chemoattraction, chemorepulsion (the movement of cells away from a stimulus) remains poorly understood. Proliferating Dictyostelium discoideum cells secrete a chemorepellent protein called AprA.

Dictyostelium discoideum cells retain nutrients when the cells are about to outgrow their food source.

Dictyostelium discoideum is a unicellular eukaryote that eats bacteria, and eventually outgrows the bacteria. D. discoideum cells accumulate extracellular polyphosphate (polyP), and the polyP concentration increases as the local cell density increases.

The extracellular sialidase NEU3 primes neutrophils.

Some extracellular glycoconjugates have sialic acid as the terminal sugar, and sialidases are enzymes that remove this sugar. Mammals have 4 sialidases and can be elevated in inflammation and fibrosis. In this report, we show that incubation of human neutrophils with the extracellular human sialidase NEU3, but not NEU1, NEU2 or NEU4, induces human male and female neutrophils to change from a round to a more amoeboid morphology, causes the primed human neutrophil markers CD11b, CD18, and CD66a to localize to the cell cortex, and decreases the localization of the unprimed human neutrophil markers CD43 and CD62-L at the cell cortex.

Sex-Based Differences in Human Neutrophil Chemorepulsion.

A considerable amount is known about how eukaryotic cells move toward an attractant, and the mechanisms are conserved from to human neutrophils. Relatively little is known about chemorepulsion, where cells move away from a repellent signal. We previously identified pathways mediating chemorepulsion in , and here we show that these pathways, including Ras, Rac, protein kinase C, PTEN, and ERK1 and 2, are required for human neutrophil chemorepulsion, and, as with chemorepulsion, PI3K and phospholipase C are not necessary, suggesting that eukaryotic chemorepulsion mechanisms are conserved.

Identification of novel proteins in the chemorepulsion pathway using REMI.

Chemorepulsion, the biased migration of a cell away from a signal, is essential for many biological processes and the ability to manipulate chemorepulsion could lead to new therapeutics for a variety of diseases. However, little is known about eukaryotic cell chemorepulsion. Utilizing the model organism we previously identified an endogenous chemorepellent protein secreted by cells called AprA, and proteins involved in the AprA-induced chemorepulsion pathway including the G protein-coupled receptor GrlH, G beta and G protein alpha 8 protein subunits, protein kinase A, components of the mammalian target of rapamycin complex 2 (mTORC2), phospholipase A, PTEN and a PTEN-like phosphatase (CnrN), a retinoblastoma orthologue (RblA), extracellular signal-regulated kinase 1 (Erk1), p-21 activated protein kinase D (PakD), and the Ras proteins RasC and RasG.

A chemorepellent inhibits local Ras activation to inhibit pseudopod formation to bias cell movement away from the chemorepellent.

The ability of cells to sense chemical gradients is essential during development, morphogenesis, and immune responses. Although much is known about chemoattraction, chemorepulsion remains poorly understood. Proliferating cells secrete a chemorepellent protein called AprA.

Using to Develop Therapeutics for Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) involves damage to lungs causing an influx of neutrophils from the blood into the lung airspaces, and the neutrophils causing further damage, which attracts more neutrophils in a vicious cycle. There are ∼190,000 cases of ARDS per year in the US, and because of the lack of therapeutics, the mortality rate is ∼40%. Repelling neutrophils out of the lung airspaces, or simply preventing neutrophil entry, is a potential therapeutic.

Extracellular signaling in Dictyostelium.

In the last few decades, we have learned a considerable amount about how eukaryotic cells communicate with each other, and what it is the cells are telling each other. The simplicity of Dictyostelium discoideum, and the wide variety of available tools to study this organism, makes it the equivalent of a hydrogen atom for cell and developmental biology. Studies using Dictyostelium have pioneered a good deal of our understanding of eukaryotic cell communication.

Reproductive Bet-Hedging and Existence in Vernal Pools as Components of Life History.

Despite the fact that has been studied for more than 200 years, we know surprisingly little about its life history. We show that embryos hatch sporadically over a period ranging from a few days to nine months. We also report, for what seems to be the first time, the presence of in a vernal pool.