Monocytic expression of CD14 and CD18, circulating adhesion molecules and inflammatory markers in women with diabetes mellitus and impaired glucose tolerance

Abstract

Aims/hypothesis. Type 2 diabetes is a major risk factor for cardiovascular disease. Monocyte recruitment and inflammatory activation are crucial steps in the development of atherosclerosis and several receptors are involved in these processes. The aim of this study was to investigate levels of CD14 and the β 2 -integrin subunits CD11b and CD18 on monocytes from women with diabetes or impaired glucose tolerance. Methods. A population-based sample of 112 Swedish women, who were aged 64 years and had diabetes mellitus or impaired or normal glucose tolerance, was investigated. Cell surface receptors were analysed with flow cytometry and serum inflammation markers and soluble adhesion molecules with enzyme-linked methods.Results. The monocytic CD14 expression and serum levels of C-reactive protein, IL-6 and soluble adhesion molecules were higher in the diabetes group than in the group with normal glucose tolerance. Monocytic CD18 was elevated both in the diabetes and in the impaired glucose tolerance groups. The levels of monocytic surface markers correlated with BMI and to a lesser extent with glycaemic control. Conclusions/interpretation. The increased monocytic expression of important surface receptors together with elevated serum inflammation markers supports the concept of increased inflammation in type 2 diabetes and may be an important factor for the risk of atherosclerosis.

Type 2 Diabetes Impairs Insulin Receptor Substrate-2-Mediated Phosphatidylinositol 3-Kinase Activity in Primary Macrophages to Induce a State of Cytokine Resistance to IL-4 in Association with Overexpression of Suppressor of Cytokine Signaling-3

“…Macrophage activation has repeatedly been shown in both human and animal studies of T2D to be altered. In human patients with T2D, circulating monocytes have increased expression of CD14 (22), which is the coreceptor for LPS. The scavenger receptor, CD36, is also up-regulated in macrophages in diabetic conditions (23).…”

High glucose enhances lipopolysaccharide-stimulated CD14 expression in U937 mononuclear cells by increasing nuclear factor κB and AP-1 activities

“…The first step for the engagement of LPS to mononuclear cells is its binding to surface CD14, a LPS receptor, and the level of CD14 surface expression is a crucial factor to determine the extent of cellular engagement by LPS (Wong et al 2000). Based on the clinical studies showing that CD14 expression by circulating mononuclear cells in patients with diabetes is higher than that in non-diabetic patients (Patino et al 2000, Fogelstrand et al 2004, we postulated that high glucose may enhance CD14 expression and thus augments the engagement of cells by LPS, leading to an increased gene expression.…”

“…Clinical studies have shown that plasma level of sCD14 is elevated in a number of inflammatory diseases such as rheumatoid arthritis (Yu et al 1998), systemic lupus erythematosus (Nockher et al 1994), atopic dermatitis (Wuthrich et al 1992), liver disease (Oesterreicher et al 1995), Kawasaki disease (Takeshita et al 2000), and atherosclerosis (Amar et al 2003). Membrane-bound CD14 expression by mononuclear cells as determined by flow cytometry was found to be higher in diabetic patients than that in non-diabetic patients (Patino et al 2000, Fogelstrand et al 2004. Obviously, all these data indicate that CD14 plays a critical role in inflammation-associated diseases.…”

Chronic Hyperglycemia Predisposes to Exaggerated Inflammatory Response and Leukocyte Dysfunction in Akita Mice

“…Levels of acute phase proteins such as IL-6 and C-reactive protein were found elevated in serum samples of diabetic women (7). Acute glucose challenge was shown to stimulate free radical release from leukocytes (8) and adipocytes (9), as well as matrix metalloproteinase 2 secretion by mononuclear cells (10).…”