Phagocytosis: Inflammation-Obesity Relationship

Obesity is a chronic, multifactorial disease with increasing worldwide prevalence. It is characterized by excessive adipose tissue accumulation in the body, which decreases the patient’s life expectancy and has been associated with a higher incidence of chronic degenerative diseases, including type 2 diabetes mellitus, systemic arterial hypertension, cancer, and cardiovascular disease. Several investigations have found that the adipose tissue of obese humans and rodents is infiltrated by a high number of macrophages. These cells interact with apoptotic adipocytes, which internalize and accumulate lipids to become foam cells. These processes lead to the release of proinflammatory mediators that promote insulin resistance. In addition, individuals with obesity have higher levels of circulating neutrophils; however, these individuals also have a higher incidence of infection, indicating that the phagocytic function of these cells is affected. This chapter describes several studies that could partly explain the phagocytic mechanisms affected by obesity. Therapeutic alternatives to favor phagocytic capacity are also discussed

Vanadyl Sulfate Effects on Systemic Profiles of Metabolic Syndrome in Old Rats with Fructose-Induced Obesity

Background. Currently, energy obtained from hypercaloric diets has been part of the obesity and type 2 diabetes mellitus (T2DM) epidemics from childhood to old age. Treatment alternatives have been sought from plants, minerals, and trace elements with metabolic effects. Vanadyl sulfate (VS) has been investigated as a hypoglycemic compound in animal and human studies showing effective insulin-mimetic properties. This characteristic encompasses several molecules that have beneficial pleiotropic effects. The aim was to determine the antiobesity, hypoglycemic, and hypolipidemic effects of VS on fructose-induced metabolic syndrome in aged rats. Material and Methods. Five groups of male Wistar rats were made, each with six rats: two groups with normal diet (ND) and three with high-fructose diet (HFD). The first ND group was treated with saline solution (SS), the second with VS; treatment for HFD groups was in the first group with SS, second with VS, and third with metformin. Weight, body mass index (BMI), blood glucose, and lipidic profile were measured; water, food, fructose and energy consumption were also determined. All parameters were compared among groups. Results and Discussion. Although obese rats treated with VS presented anorexia, oligodipsia, and a marked weight loss in the first two weeks. They recovered food and water intake in the third week with a slow recovery of some weight weeks later. VS normalized blood glucose level and decreased triglyceride and insulin levels in obese rats. These results suggest that vanadyl sulfate shows antiobesity, hypoglycemic, and hypolipidemic properties in old obese rats and could be useful as an alternative, additional, and potent preventive treatment for obesity and T2DM control in elderly obese and poorly controlled diabetic patients. Conclusion. VS could play an important role in the treatment of metabolic syndrome, contributing to a decrease in obesity and T2DM, through different ways, such as euglycemia, satiety, weight loss, and lipid profile optimization, among others. However, more research is needed to confirm this suggestion

Low Expression of IL-10 in Circulating Bregs and Inverted IL-10/TNF-α Ratio in Tears of Patients with Perennial Allergic Conjunctivitis: A Preliminary Study

Allergic conjunctivitis (AC) is one of the most common ophthalmological disorders seen in clinical practice. Growing evidence from recent years suggests that a subset of IL-10-expressing B cells is involved in inflammatory allergic diseases. In this study, we aimed to evaluate the potential involvement of blood Bregs cells in perennial allergic conjunctivitis (PAC), and interleukins (IL)-1β, IL-6, IL-8, IL-10, and IL-12, and tumor necrosis factor (TNF)-α, were measured in tear samples and compared with healthy controls (HC) using flow cytometry. Non-significant differences in CD19+IL-10+ cell frequency between PAC patients and healthy controls (HC) were observed. Nevertheless, when we analyzed the mean fluorescence intensity (MFI) of IL-10 on CD19+CD38Lo/Med/Hi-gated cells, we observed a significant decrease in MFI in all Bregs subsets in PAC patients. Additionally, tear cytokines showed 2.8 times lower levels of IL-10 than TNF-α in PAC patients when compared to HC. Our findings demonstrate an immunological dysregulation in patients with allergic conjunctivitis, characterized by the low expression of IL-10 in circulating CD19+CD38+ Bregs subsets and an inverted tear IL-10/TNF-α ratio, promoting a local pro-inflammatory microenvironment. These findings highlight the novel pathologic changes involved in ocular allergic diseases. Understanding systemic and local mechanisms will aid the design of immunomodulating therapeutics at different levels

Nonbilayer Phospholipid Arrangements Are Toll-Like Receptor-2/6 and TLR-4 Agonists and Trigger Inflammation in a Mouse Model Resembling Human Lupus

Systemic lupus erythematosus is characterized by dysregulated activation of T and B cells and autoantibodies to nuclear antigens and, in some cases, lipid antigens. Liposomes with nonbilayer phospholipid arrangements induce a disease resembling human lupus in mice, including IgM and IgG antibodies against nonbilayer phospholipid arrangements. As the effect of these liposomes on the innate immune response is unknown and innate immune system activation is necessary for efficient antibody formation, we evaluated the effect of these liposomes on Toll-like receptor (TLR) signaling, cytokine production, proinflammatory gene expression, and T, NKT, dendritic, and B cells. Liposomes induce TLR-4- and, to a lesser extent, TLR-2/TLR-6-dependent signaling in TLR-expressing human embryonic kidney (HEK) cells and bone marrow-derived macrophages. Mice with the lupus-like disease had increased serum concentrations of proinflammatory cytokines, C3a and C5a; they also had more TLR-4-expressing splenocytes, a higher expression of genes associated with TRIF-dependent TLR-4-signaling and complement activation, and a lower expression of apoptosis-related genes, compared to healthy mice. The percentage of NKT and the percentage and activation of dendritic and B2 cells were also increased. Thus, TLR-4 and TLR-2/TLR-6 activation by nonbilayer phospholipid arrangements triggers an inflammatory response that could contribute to autoantibody production and the generation of a lupus-like disease in mice

Human platelets and megakaryocytes express defensin alpha 1

Platelets are anucleate cells that have a role in several innate immune functions, including the secretion of proteins with antimicrobial activity. Several studies have demonstrated the ability of platelets to secrete thrombin-induced platelet microbicidal proteins and antimicrobial peptides, like hBD-1. However, the expression and secretion of defensins of the alpha family by platelets have not been fully elucidated. The aim of this study was to characterize the expression of defensin alpha 1 (DEFA1) in human platelets and megakaryocytes. Our data indicate that DEFA1 mRNA and protein are present in peripheral blood platelets and in the megakaryoblastic leukemia cell line (MEG-01). DEFA1 co-localize with α-granules of platelets and MEG-01 cells, and was also detected in cytoplasm of MEG-01 cells. The assay of our in vitro model of platelet-like particles (PLPs) revealed that MEG-01 cells could transfer DEFA1 mRNA to their differentiated PLPs. Furthermore, platelets secreted DEFA1 into the culture medium when activated with thrombin, adenosine diphosphate, and lipopolysaccharide; meanwhile, MEG-01 cells secreted DEFA1 when activated with thrombopoietin. Platelet’s secreted DEFA1 can rebind to platelet’s surface and have antibacterial activity against the gram-negative bacteria Escherichia coli. In summary, our data indicate that both, human platelets and megakaryocytes, can express and secrete DEFA1. These results suggest a new role of platelets and megakaryocytes in the innate immune response