Influence of glutamine on the phenotype and function of human monocytes

Abstract

Reduced concentrations of glutamine (GLN) in plasma and skeletal muscle, defective host defense systems, and a diminished expression of the HLA-DR antigen on monocytes are important diagnostic parameters for late post-injury sepsis. In this in vitro study, we investigated whether blood monocyte-derived macrophage antigen expression and function from healthy donors is influenced by GLN. Lowering the GLN concentration in culture medium from 2 mmol/L to 200 mumol/L reduced the expression of HLA-DR by 40% (P < .001) on monocyte-derived macrophages, and decreased tetanus toxoid-induced antigen presentation. In addition, low GLN levels downregulated the expression of intercellular adhesion molecule-1 (ICAM-1/CD54), Fc receptor for IgG (Fc gamma RI/CD64), and complement receptors type 3 (CR3; CD11b/CD18) and type 4 (CR4; CD11c/CD18). A correlation was found between the phagocytosis of IgG-sensitized ox erythrocytes or opsonized Escherichia coli and the decreased expression of Fc gamma RI and CR3. Monocyte expression of CD14, CD71, and Fc gamma RIII/CD16 and capacity to phagocytose latex beads were not affected by altering the level of GLN. Depletion of GLN was associated with a significant reduction in cellular adenosine triphosphate (ATP), which may have influenced cell surface marker expression and phagocytosis. It remains to be seen whether these in vitro findings are of clinical significance in the treatment of sepsis.

Immunomodulatory effects of glycine on LPS‐treated monocytes: reduced TNF‐α production and accelerated IL‐10 expression

“…Correction for discrepancies in loading (␤-actin) were made; changes in the level of IL-1␤ and TNF-␣-specific mRNA vs. control are shown in percentages. pression on peripheral blood monocytes (19). Furthermore, these effects correlated with an increased capacity to present antigen and to phagocytose.…”

“…Monocytes (2ϫ10 5 ) and beads (8ϫ10 6 ) were incubated for 1 h at 37°C, centrifuged, and washed. The percentage of CD14 ϩ monocytes ingesting E. coli was analyzed by FACS (19).…”

“…Recent studies have shown that a supply of the amino acid glutamine in pharmacological quantities was able to reduce mortality in intensive care unit patients, possibly via an influence on monocyte phenotype and function (17)(18)(19). Enteral adminis-tration of glycine (GLY) decreased the release of TNF-␣ from isolated Kupffer cells almost completely and significantly reduced mortality in an experimental model of endotoxemia (20).…”

Cellular metabolism of myeloid cells in sepsis

“…Interestingly, however, monocyte-derived macrophages showed lower HLA-DR, ICAM-1, FcgR, and CR3 and CR4 expression after lowering glutamine concentration in the culture medium. In addition, intracellular ATP concentrations were reduced [120]. Others have reported an induction of cytokine production after glutamine supplementation in LPS-induced acute lung injury [121] or different effects in vitro (increased TNF-a production) versus in vivo (decrease) of macrophages [122].…”

Glutamine as an Immunoenhancing Nutrient

“…Glutamine is essential for the function of immune cells, especially lymphocytes and macrophages. [11][12][13][14][15] Glutamine supplementation may provide respiratory substrate and a nucleotide precursor to these immune cells.2 Through this mechanism, glutamine supplementation can modulate the immune function of lymphocytes and macrophages.…”