title: Human Serum Albumin (HSA) Suppresses the Effects of Glycerol Monolaurate (GML) on Human T Cell Activation and Function.
abstract: Glycerol monolaurate (GML) is a monoglyceride with well characterized anti-microbial properties. Because of these properties, GML is widely used in food, cosmetics, and personal care products and currently being tested as a therapeutic for menstrual associated toxic shock syndrome, superficial wound infections, and HIV transmission. Recently, we have described that GML potently suppresses select T cell receptor (TCR)-induced signaling events, leading to reduced human T cell effector functions. However, how soluble host factors present in the blood and at sites of infection affect GML-mediated human T cell suppression is unknown. In this study, we have characterized how human serum albumin (HSA) affects GML-induced inhibition of human T cells. We found that HSA and other serum albumins bind to 12 carbon acyl side chain of GML at low micromolar affinities and restores the TCR-induced formation of LAT, PLC-γ1, and AKT microclusters at the plasma membrane. Additionally, HSA reverses GML mediated inhibition of AKT phosphorylation and partially restores cytokine production in GML treated cells. Our data reveal that HSA, one of the most abundant proteins in the human serum and at sites of infections, potently reverses the suppression of human T cells by GML. This suggests that GML-driven human T cell suppression depends upon the local tissue environment, with albumin concentration being a major determinant of GML function.
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, United States of America.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, United States of America.
authors.forename: Jon C D
authors.initials: JC
authors.lastname: Houtman
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007848:Laurates / Q000009:adverse effects* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008565:Membrane Proteins / Q000378:metabolism; D050178:Monoglycerides / Q000009:adverse effects* / Q000494:pharmacology; D051966:Phospholipase C gamma / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012709:Serum Albumin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; C110810:LAT protein, human; D007848:Laurates; D008565:Membrane Proteins; D050178:Monoglycerides; D012709:Serum Albumin; C020777:monolaurin; D051057:Proto-Oncogene Proteins c-akt; D051966:Phospholipase C gamma