Carbohydrate Metabolism by Leukocytes

Stjernholm, R.; Burns, C. Patrick; Hohnadel, J H

doi:10.1159/000459647

Cited by 51 publications

(18 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Intracellular killing of bacteria requires lysosomal migration to and fusion with bacteria containing phagosomes (36). A sequence of metabolic events is associated with this event including the enzymatic generation of peroxide and stimulation of the HMP shunt (37). The observation that HCS did not prevent stimulation of HMP shunt activity of monocytes after ingestion of latex particles suggests that the metabolic pathways involved in peroxide generation and HMP shunt response are not directly inhibited.…”

Section: Discussionmentioning

confidence: 99%

Effects of Corticosteroids on Human Monocyte Function

Rinehart¹,

Balcerzak²,

Sagone³

et al. 1974

J. Clin. Invest.

241

View full text Add to dashboard Cite

A B S T R A C T This report examined the effect of corticosteroids in vitro on human peripheral blood monocytes, essential cells in both immune and nonimmune cellular defense mechanisms. Monocyte chemotaxis in response to sera, Escherichia coli filtrate, and lymphokine chemotactic factor was markedly reduced (P < 0.01) by hydrocortisone succinate (HCS) at 16 Ag/ml. Methylprednisolone succinate and unesterified hydrocortisone produced similar impairment of monocyte chemotaxis while two drugs which unmodified do not enter cells, hydrocortisone phosphate (HCP) and cortisone acetate, had no effect on chemotaxis. HCS also significantly impaired monocyte random migration at 16 jug/ml. Monocyte bactericidal activity was reduced by HCS at 16 Ag/ml (P < 0.01) ) but was not affected by HCP even at 120 Lg/ml. In comparison, HCS did not alter granulocyte chemotaxis even at 500 Ag/ml, and bactericidal activity was reduced at 16 jg/ml (P < 0.01). Monocyte phagocytosis of cryptococci was reduced only 20% (P < 0.05) at 120 Ag/ml. HCS at 120 Ag/ml did not alter monocyte base-line or postphagocytic hexosemonophosphate shunt activity, viability by trypan blue exclusion, adherence to tissue culture flasks, or surface binding of IgG globulin. These corticosteroid-induced defects in monocyte function may contribute to reduced cellular defense during corticosteroid therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of Corticosteroids on Human Monocyte Function

Rinehart¹,

Balcerzak²,

Sagone³

et al. 1974

J. Clin. Invest.

241

View full text Add to dashboard Cite

show abstract

“…neutrophils are known to require a constant supply of glucose for their function and survival and are unable to produce glucose via gluconeogenesis. 58 The primary source of glucose, therefore, is the circulating blood. Consistent with this notion, neutrophils from patients with GSD-Ib have a decreased rate of glucose transport across the cell membrane, 59 which results in intracellular concentrations of G6P that are only 25% of normal levels, even in the presence of exogenous glucose.…”

Section: Phenotypementioning

confidence: 99%

Glycogen storage disease type I and G6Pase-β deficiency: etiology and therapy

2010

View full text Add to dashboard Cite

Glycogen storage disease type I (GSD-I) consists of two subtypes: GSD-Ia, a deficiency in glucose-6- phosphatase-α (G6Pase-α) and GSD-Ib, which is characterized by an absence of a glucose-6-phosphate (G6P) transporter (G6PT). A third disorder, G6Pase-β deficiency, shares similarities with this group of diseases. G6Pase-α and G6Pase-β are G6P hydrolases in the membrane of the endoplasmic reticulum, which depend on G6PT to transport G6P from the cytoplasm into the lumen. A functional complex of G6PT and G6Pase-α maintains interprandial glucose homeostasis, whereas G6PT and G6Pase-β act in conjunction to maintain neutrophil function and homeostasis. Patients with GSD-Ia and those with GSD-Ib exhibit a common metabolic phenotype of disturbed glucose homeostasis that is not evident in patients with G6Pase-β deficiency. Patients with a deficiency in G6PT and those lacking G6Pase-β display a common myeloid phenotype that is not shared by patients with GSD-Ia. Previous studies have shown that neutrophils express the complex of G6PT and G6Pase-β to produce endogenous glucose. Inactivation of either G6PT or G6Pase-β increases neutrophil apoptosis, which underlies, at least in part, neutrophil loss (neutropenia) and dysfunction in GSD-Ib and G6Pase-β deficiency. Dietary and/or granulocyte colony-stimulating factor therapies are available; however, many aspects of the diseases are still poorly understood. This Review will address the etiology of GSD-Ia, GSD-Ib and G6Pase-β deficiency and highlight advances in diagnosis and new treatment approaches, including gene therapy.

show abstract

“…Neutrophils cannot produce glucose via gluconeogenesis, 15 and their glucose is supplied by uptake from the blood mediated by the glucose transporters (GLUTs). 16 Within neutrophils, glucose is metabolized by hexokinase (HK) to G6P.…”

Section: Introductionmentioning

confidence: 99%

Molecular mechanisms of neutrophil dysfunction in glycogen storage disease type Ib

Jun

Weinstein

Lee

et al. 2014

Blood

106

133

View full text Add to dashboard Cite

• A deficiency in G6PT impairs neutrophil energy homeostasis characterized by reduced intracellular levels of G6P, ATP, lactate, and NADPH. • Impaired energy homeostasis and activation of the HIF-1a/ PPAR-g pathway underlie neutrophil dysfunction in GSD-Ib.Glycogen storage disease type Ib (GSD-Ib) is an autosomal-recessive syndrome characterized by neutropenia and impaired glucose homeostasis resulting from a deficiency in the glucose-6-phosphate (G6P) transporter (G6PT). The underlying cause of GSD-Ib neutropenia is an enhanced neutrophil apoptosis, but patients also manifest neutrophil dysfunction of unknown etiology. Previously, we showed G6PT interacts with the enzyme glucose-6-phosphatase-b (G6Pase-b) to regulate the availability of G6P/ glucose in neutrophils. A deficiency in G6Pase-b activity in neutrophils impairs both their energy homeostasis and function. We now show that G6PT-deficient neutrophils from GSD-Ib patients are similarly impaired. Their energy impairment is characterized by decreased glucose uptake and reduced levels of intracellular G6P, lactate, adenosine triphosphate, and reduced NAD phosphate, whereas functional impairment is reflected in reduced neutrophil respiratory burst, chemotaxis, and calcium mobilization. We further show that the mechanism of neutrophil dysfunction in GSD-Ib arises from activation of the hypoxia-inducible factor-1a/peroxisome-proliferators-activated receptor-g pathway.

show abstract

Carbohydrate Metabolism by Leukocytes

Abstract: This review is aimed at describing biochemical activities of human white cells with emphasis on carbohydrate metabolism. Recent efforts directed toward a search for differences in intermediary metabolism between normal and leukemic leukocytes are included.

Cited by 51 publications

References 47 publications

Effects of Corticosteroids on Human Monocyte Function

Effects of Corticosteroids on Human Monocyte Function

Glycogen storage disease type I and G6Pase-β deficiency: etiology and therapy

Molecular mechanisms of neutrophil dysfunction in glycogen storage disease type Ib

Contact Info

Product

Resources

About