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Inhibitory action of D-galactose on phagocyte metabolism and function
Abstract:
To account for enhanced susceptibility to infection among galactosemics, the acute effects of D-galactose on metabolic and functional activities of phagocytic cells in vitro were investigated. Human and guinea pig polymorphonuclear leukocytes (PMN) when incubated in medium containing 30 mM galactose displayed substantially less killing of Escherichia coli than when incubated in medium with 5 mM glucose. Impaired bactericidal activity was dependent upon galactose concentration but could be partially averted by supplementing the galactose-containing medium with 15 mM glucose. Phagocytic activities of guinea pig PMN and peritoneal macrophages were assayed by following ingestion of 32P-labeled E. coli and were also depressed by elevated galactose. Galactose was readily epimerized to glucose by resting PMN, and this conversion was stimulated by phagocytosis. Incubation of macrophages in the presence of galactose resulted in depletion of intracellular levels of adenosine 5' -triphosphate as well as other metabolities.
Insights
High galactose levels impair phagocytic cell function, reducing the ability to fight infections like Escherichia coli. Supplementing with glucose can partially restore this immune cell activity.
Area of Science:
- Immunology
- Metabolic Biochemistry
Background:
- Galactosemia is associated with increased infection susceptibility.
- The precise mechanisms underlying this immune deficiency require elucidation.
Purpose of the Study:
- To investigate the in vitro effects of D-galactose on phagocytic cell function.
- To determine the impact of galactose on the metabolic and bactericidal activities of human and guinea pig phagocytes.
Main Methods:
- Incubation of human and guinea pig polymorphonuclear leukocytes (PMN) and macrophages with varying concentrations of D-galactose and glucose.
- Assaying bacterial killing of Escherichia coli by PMN.
- Measuring the ingestion of 32P-labeled E. coli by PMN and macrophages.
- Monitoring the epimerization of galactose to glucose by PMN.
- Quantifying intracellular metabolite levels, including adenosine 5'-triphosphate, in macrophages.
Main Results:
- Elevated galactose (30 mM) significantly reduced the killing of Escherichia coli by human and guinea pig PMN compared to glucose (5 mM).
- Impaired bactericidal activity was dose-dependent and partially reversible with glucose supplementation.
- Galactose also depressed the phagocytic activity of guinea pig PMN and macrophages.
- PMN converted galactose to glucose, a process enhanced during phagocytosis.
- Macrophage incubation with galactose led to depletion of intracellular adenosine 5'-triphosphate and other metabolites.
Conclusions:
- D-galactose acutely impairs the metabolic and functional capacity of phagocytic cells, contributing to enhanced infection susceptibility in galactosemia.
- These findings highlight a direct cellular mechanism linking galactose metabolism to immune dysfunction.