In vitro alteration of macrophage phenotype and function by serum lipids

Abstract

Diabetes (type I and type II) affects approximately 13 million people in the United States. Delayed and incomplete healing of wounds can be a major problem for diabetic patients. Macrophages are an important cell in the complex process of wound repair representing the major source of cytokines throughout the wound-healing process. Cytokines mediate many of the cellular responses critical to timely wound repair. It has been suggested that diabetes impairs wound healing through disruption of local cytokine production. Our previous in vivo studies in rats demonstrated that diabetes-induced and diet-induced hyperlipidemia cause changes in macrophage phenotype and function (Iacopino 1995; Doxey et al. 1998), suggesting that alterations in macrophage cytokine profiles represent the cellular/molecular mechanism responsible for delayed wound healing. The purpose of this study was to investigate how monocyte maturation/differentiation and cytokine production were altered by serum lipids in an in vitro system using human cells. Commercially prepared purified human monocytes were cultured and exposed to serum lipids. Phenotypic analysis of differentiated macrophages was then performed by flow cytometry and fluorescent microscopy using surface antigens specific for various macrophage subsets. Selected cytokines in conditioned medium were assayed using commercial human enzyme-linked immunosorbent assay (ELISA) kits. We demonstrate that serum lipids cause an increase in monocytic differentiation leading to an inflammatory macrophage phenotype rather than a reparative/proliferative phenotype. We also show that serum lipids cause a generalized decrease in macrophage cytokine production using interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), platelet-derived growth factor (PDGF), and transforming growth factor beta 1 (TGF-beta 1) as marker cytokines. Our present in vitro results using human cells confirm our previous in vivo studies in the rat and support the hypothesis that diabetes-induced hyperlipidemia alters the monocyte differentiation process resulting in changes of macrophage subsets and cytokine release at the wound site, ultimately impairing the wound-healing process.

Profiling changes triggered during maturation of dendritic cells: a lipidomic approach

“…The proportion of polyunsaturated fatty acid in both cases is much lower than in normal cells. Moreover, cells in vivo are most likely to have very different PUFA composition, as shown recently for neuronal stem cells [47], and the composition is dependent on nutrition [48,49] and phenotype [50]. Thus, further in-vivo studies are needed to validate the results presented in this manuscript.…”

Genomic structure, chromosomal localization and expression profile of a novel melanoma differentiation associated (mda-7) gene with cancer specific growth suppressing and apoptosis inducing properties

“…Di erentiation of K562 leukemia cells by TPA treatment to megakaryocytic cells is characterized by an increase in platelet peroxidase positivity, enhancement of thromboxane A2 receptors and increased cell volume and DNA ploidy (reviewed in Alitalo, 1990). There is also an increase in synthesis of platelet derived growth factor (PDGF) and transforming growth factor beta 1 (TGF-b1) two of the cytokines that mark the wound-healing process (Chu et al, 1999;Li et al, 1999;Miller, 1999). The molecular function of mda-7 during this program of di erentia- : IFN-b+MEZ tion is unclear at this time, however, it is possible that mda-7 may have multiple biological roles including an involvement in immune responses and wound healing.…”

Is there a relationship between hyperlipidemia and periodontitis?

“…The cycle may begin with the elevation of serum lipid levels or with the presence of periodontitis, both of which may lead to further elevation of serum proinflammatory cytokine levels causing an exaggerated tissue response that lasts with more severe periodontitis, metabolic disturbances and systemic diseases. [8][9][10]26,43,53,54 It is noteworthy that both hyperlipidemia and periodontitis are risk factors for CVD which is the number one cause of death worldwide.…”

“…7,37 Direct interaction between lipids and macrophage cell membrane can alter the periodontal disease associated growth factor and proinflammatory cytokine expression. 31,43 Moreover, hyperlipidemia may be more essential compared to hyperglycemia in relation to the hyper responsive monocytic phenotype in periodontal diseases. 31,[44][45][46] In this cross-sectional study, we aimed to investigate any interaction/association between hyperlipidemia and periodontal disease regarding the periodontal parameters together with age, gender, body mass index (BMI), dietary habit, physical activity, alcohol consumption and plasma lipid parameters.…”