Influence of Glucose Levels on the In Vitro Phagocytosis of Bacteria by Human Neutrophils

Abstract

A previously developed in vitro method for studying the phagocytosis of bacteria and particles by human neutrophils was used to investigate the influence of different glucose levels on phagocytosis. It was found that high glucose levels (200, 400, and 800 mg ofglucose/100 ml) significantly depressed the phagocytosis ofStaphylococcus epidermidis, S. aureus, and Escherichia coli. At very low glucose levels, a somewhat decreased phagocytic activity was noted. The strongest phagocytic activity occurred at glucose concentrations of 50 and 100 mg/100 ml. A second effect noted at the higher (200, 400 and 800 mg/100 ml) glucose concentrations was a decreased adhesiveness of the neutrophils to solid surfaces. The mechanism of the decrease in phagocytosis and in neutrophil adhesiveness at higher glucose levels is unknown, but it is not linked to increased osmotic pressures due to the presence of glucose, as ethanol, at the same and even higher osmolal concentrations, had no effect on the phagocytosis. These results show that not only the phagocytic activity of those neutrophils that do adhere to a solid surface is diminished at higher glucose concentrations but also that fewer neutrophils adhere to solid surfaces at higher glucose levels. These two phenomena combined may provide at least part of the explanation for the well-known decrease in resistance to bacterial infections of diabetics.

The influence of blood glucose on neutrophil function in individuals without diabetes

“…Various studies have reported that hyperglycemia decreases neutrophil function (stimulated ROS production and PA) , while others have reported an increase in ROS production in individuals with diabetes mellitus . These contradictory results were similar in individuals without diabetes . The results of previous studies do not agree with ours because of the low number of subjects and the use of isolated neutrophils in those studies.…”

“…However, many studies on stimulated ROS production of neutrophils under hyperglycemic conditions in prediabetic participants have reported conflicting results. For example, some studies found that hyperglycemia decreased neutrophil function in prediabetic subjects, whereas others found that hyperglycemia had no effect on neutrophil function . Furthermore, basal ROS production under hyperglycemic conditions in prediabetic individuals without diabetes has not been reported.…”

Ingestion of yeast forms of Sporothrix schenckii by mouse peritoneal macrophages

“…At a 10mg/ml sugar concentration, macrophages kept unaltered their capacity to phagocytize latex particles or sensitized sheep erythrocytes. The inhibitory activity of simple sugars on the phagocytosis of S. schenckii cannot thus be attributed to functional alterations of macrophages as suggested by others with high levels of sucrose and hyperglycemic concentrations of glucose (18,25). The exposure of macrophage cultures for 24 h to several neutral monosaccharides at 10 to 20 mg/ml, including pentoses, glucose, and galac- tose, irrespective of whether they were metabolizable by the cells, was not followed by vacuolization.…”

Hyperglycemia‐Induced Protein Kinase C Activation Inhibits Phagocytosis of C3b‐ and Immunoglobulin G–Opsonized Yeast Particles in Normal Human Neutrophils

“…Phagocytosis is a complicated process that can be activated by several different types of prophagocytic receptors, where two of the best characterized are Fcγ receptors for the Fc portion of immunoglobulin G (IgG) on IgGopsonized targets and complement receptor 3 (CR3) that will recognize C3bi-opsonized targets [8]. Conflicting data have been reported about the in vitro phagocytic capacity of neutrophils from patients with diabetes mellitus, showing both normal [5][6][7] as well as decreased phagocytosis activity [2,[9][10][11]. Interestingly, increased glucose concentrations were found to impair phagocytosis of IgG-opsonized Staphylococcus aureus by normal human neutrophils [12], whereas phagocytosis of C3bi-opsonized Staphylococcus aureus was unaffected by elevated glucose concentrations [13].…”