Biology subjects

Kirolos, S. A.

Publications and source records attributed to Kirolos, S. A..

3 recordsLinked to original sources

bioRxiv2025

Differences between human male and female neutrophils with respect to which RNAs are present in polysomes

BackgroundHuman males and females show differences in the incidence of neutrophil-associated diseases such as systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis, and differences in neutrophil physiological responses such as responses to infection, tissue damage, and chemotactic factors. However, little is known about the basis of sex-based differences in human neutrophils. MethodsStarting with human neutrophils from healthy donors, we used RNA-seq to examine total RNA profiles, RNAs not associated with ribosomes and thus not being translated, RNAs in monosomes, and RNAs in polysomes and thus heavily translated. ResultsThere were sex-based differences in the levels of RNAs across free RNA, monosome, and polysome fractions. Male neutrophils had increased levels of mRNAs encoding mitochondrial proteins in the free RNA fractions, indicating low levels of translation. The polysomes of male neutrophils were enriched for mRNAs encoding cytoskeletal organization, cell motility, and cell activation. The polysomes of female neutrophils were enriched for mRNAs associated the regulation of metabolic processes, cytokine responses, and mitochondrial proteins. ConclusionsThese data indicate that male and female neutrophils have different expression patterns and different translation efficiency of some mRNAs. This may contribute to the observed sex-based differences in neutrophil behavior and neutrophil-associated disease incidence and severity.

immunology↗

bioRxiv2022

Dictyostelium discoideum cells sense their local density and retain nutrients when the cells are about to overgrow their food source

Dictyostelium discoideum is a unicellular eukaryote that eats bacteria, and eventually overgrows the bacteria. D. discoideum cells accumulate extracellular polyphosphate (polyP), and the polyP concentration increases as the local cell density increases. At high cell densities, the correspondingly high extracellular polyP concentrations allow cells to sense that they are about to overgrow their food supply and starve, causing the D. discoideum cells to inhibt their proliferation. In this report, we show that high extracellular polyP inhibits exocytosis of undigested or partially digested nutrients. PolyP decreases cell membrane fluidity and plasma membrane recycling, and this requires the G protein-coupled polyP receptor GrlD, the polyphosphate kinase Ppk1, and the inositol hexakisphosphate kinase I6kA. PolyP did not affect random cell motility, cell speed, or F-actin levels. PolyP decreased membrane saturated fatty acids and altered lipid and protein contents in detergent-insoluble lipid microdomains. Together, these data suggest that D. discoideum cells use polyP as a signal to sense their local cell density and reduce cell membrane fluidity and membrane recycling, perhaps as a mechanism to retain ingested food when the cells are about to starve.

cell biology↗

bioRxiv2022

The extracellular sialidase NEU3 induces neutrophil priming

Some extracellular glycoconjugates have sialic acid as the terminal sugar, and sialidases are enzymes that remove this sugar. Mammals have four sialidases, but their biological functions are unclear. In this report, we show that incubation of human neutrophils with the human sialidase NEU3, but not NEU1, NEU2 or NEU4, inducess human male and female neutrophils to change from a round to a more amoeboid morphology, causes the primed neutrophil markers CD66, CD11B, and CD18 to localize to the cell cortex, and decreases the localization of the unprimed neutrophil markers CD43 and CD62L at the cell cortex. NEU3, but not the other 3 sialidases, also causes human male and female neutrophils to increase their F-actin content. The inhibition of NEU3 by the NEU3 inhibitor 2-acetylpyridine attenuated the NEU3 effect on neutrophil morphology, indicating that the effect of NEU3 is dependent on its enzymatic activity. Together, these results indicate that NEU3 can prime human male and female neutrophils, and that NEU3 is a potential regulator of inflammation.

immunology↗