Dr Katharine Martin - Inflammation division

Dr Katharine Martin - Inflammation division

Location: 
Online
Start Time: 
Wed, 27/10/2021 - 1:00pm
End Time: 
Wed, 27/10/2021 - 2:00pm

WEHI Wednesday Seminar hosted by Professor Ian Wicks

 

Dr Katherine Martin

Research Officer - Wicks Lab, Inflammation division -  Infection, Inflammation & Immunity Theme

 

Understanding how pathogenic low density neutrophils contribute to disease

 

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Including Q&A session

 

Low density neutrophils (LDN) are rarely detected in healthy people but appear in the peripheral blood (PB) of individuals treated with granulocyte colony-stimulating factor (G-CSF) and in patients with inflammatory diseases and malignancies. LDN co-purify with mononuclear cells during density-gradient separation of peripheral blood. Using human G-CSF mobilized LDN, we show that LDN are transcriptionally, proteomically and metabolically distinct from other neutrophil populations. Whole cell proteomics revealed that CD98 was significantly upregulated in LDN. CD98 is a type II transmembrane protein which dimerizes with several L-type amino acid transporters to facilitate uptake of essential amino acids. We demonstrate that expression of CD98 is increased on LDN and can be used as a phenotypic marker to detect LDN in the blood of patients with system lupus erythematosus, and within the blood and tumour tissue of cancer patients. We present functional evidence that CD98 is responsible for the increased bioenergetic capacity of LDN. Upregulation of CD98 on LDN facilitates the uptake of amino acids that are subsequently used by the mitochondria as fuel to produce ATP in the absence of glucose. We show that pharmacological inhibition of CD98 reduces the metabolic flexibility of LDN, which may in turn limit the pathogenic capacity of this neutrophil subset.

 



All welcome!