Abstract
Hypertension is accompanied by the over-activation of macrophages. Diuretics administered alone or in combination with hypotensive drugs may have immunomodulatory effects. Thus, the influence of tested drugs on mouse macrophage-mediated humoral immunity was investigated. Mice were treated intraperitoneally with captopril (5 mg/kg) with or without hydrochlorothiazide (10 mg/kg) or furosemide (5 mg/kg) by 8 days. Mineral oil-induced peritoneal macrophages were harvested to assess the generation of cytokines in ELISA, and the expression of surface markers was analyzed cytometrically. Macrophages were also pulsed with sheep red blood cells (SRBC) and transferred to naive mice for evaluation of their ability to induce a humoral immune response. Tested drugs increase the expression of surface markers important for the antigen phagocytosis and presentation. SRBC-pulsed macrophages from mice treated with captopril combined with diuretics increased the secretion of antigen-specific antibodies by recipient B cells, while macrophages of mice treated with hydrochlorothiazide or furosemide with captopril increased the number of antigen-specific B cells. Tested drugs alter the macrophage secretory profile in favor of anti-inflammatory cytokines. Our results showed that diuretics with or without captopril modulate the humoral response by affecting the function of macrophages, which has significant translational potential in assessing the safety of antihypertensive therapy.
Highlights
Macrophages mainly function as phagocytes that may present antigens to induce the adaptive humoral and cellular immune responses
The producing cells in plaque-forming assay (PFA), in sera and spleens obtained from recipient specific antibody titers were measured in hemagglutination assay, and the number mice 7 days after macrophage transfer
Our studies have shown that hydrochlorothiazide slightly increases the concentration of the pro-inflammatory cytokine TNFα, adding captopril causes a significant reduction in the production of TNFα
Summary
Macrophages mainly function as phagocytes that may present antigens to induce the adaptive humoral and cellular immune responses. These cells play an important role in various other processes that are essential to maintain the body’s homeostasis, such as tissue repair and regeneration. On the other hand, dysregulated macrophage activity is observed in different disorders, including cardiovascular diseases [1]. Macrophages are currently considered promising cellular targets for selective drug delivery [2,3]. Macrophages may bind and react to drug-derived bioactive compounds due to the expression of various receptors on both plasma membrane and intracellular membranes, as well as may sense and react to microenvironmental changes induced by the particular medication [2].
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