The Increase in CD14+CD16+ Monocytes is Correlated with Cardiovascular Disease Risk Marker in Type 2 Diabetes

Ujang Saeful Hikmat, Ani Retno Prijanti, Heri Wibowo, Indriyanti Rafi Sukmawati, Dicky Levenus Tahapary

Abstract


BACKGROUND: Type 2 Diabetes (T2D) impairs the innate immune system including monocytes. Monocytes are divided into two subgroups depending on the expression of cluster of differentiation (CD)14 and CD16 receptors, namely CD14+CD16- and CD14+CD16+. CD14+CD16+ are proinflammatory monocytes and develop into M1 type macrophages, which contribute to foam cell production, a risk factor for cardiovascular disease (CVD). Therefore, it is important to determine the influence of T2D conditions on changes in monocyte subsets and whether these changes correlate with CVD risk markers.

METHODS: Peripheral blood mononuclear cell (PBMC) was obtained from 10 T2D subjects and 10 healthy donors. Subsequently, PBMC was incubated for 24 hours with and without 10 mL lipopolysaccharide. Flow cytometry was used to evaluate CD14 and CD16 expression, while multiplex immunoassays were applied to measure interleukin (IL)-1b and IL-10 concentrations in supernatants.

RESULTS: In T2D, the percentage of CD14+CD16+ monocytes increased (p=0.07), and an increase in CD14+CD16+ monocytes more than 6.8% was linked with CVD risk markers (r=10.146, p=0.002). Meanwhile, inflammatory mediators released by monocytes shown an increase in IL-1b (p=0.041) but not in IL-10 (p=0.082) in T2D subjects. Fasting blood glucose levels were also found to be substantially linked with an increase in CD14+CD16+ monocytes (r=0.530, p=0.016).

CONCLUSION: T2D patients had a higher percentage of CD14+CD16+ monocytes and IL-1b levels than healthy donors. An increase in CD14+CD16+ monocytes above 6.8% associated with CVD risk markers in T2D patients.

KEYWORDS: type 2 diabetes, monocytes, CD14, CD16, cardiovaskular disease risk marker


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References


International Diabetes Federation (IDF). IDF Diabetes Atlas. 7th ed. Brussels: IDF; 2015, article.

World Health Organization (WHO). Diabetes is on The Rise. Geneva: WHO; 2021.

Kirtaniya AAIK, Lestarini A, Permatananda PANK, Aryastuti AASA. Association of ELMO1 genetic polymorphism (rs741301) with the progression of diabetic kidney disease in balinese patients with type 2 diabetes mellitus. Mol Cell Biomed Sci. 2023; 7(1): 47-51, CrossRef.

Stitt AW, Jenkins AJ, Cooper ME. Advanced glycation end products and diabetic complications. Expert Opin Investig Drugs. 2002; 11(9): 1205-23, CrossRef.

Limantara E, Kartawidjajaputra F, Suwanto A. Evaluation of potential gene expression as early markers of insulin resistance and non-alcoholic fatty liver disease in the Indonesian population. Indones J Biotechnol. 2018; 23(2): 84-90, CrossRef.

Tursinawati Y, Hakim RF, Rohmani A, Kartikadewi A, Sandra F. CAPN10 SNP-19 is associated with susceptibility of type 2 diabetes mellitus: A javanese case-control study. Indones Biomed J. 2020; 12(2): 109-14, CrossRef.

Jagannathan R, Thayman M, Rao SR. Proinflammatory (CD14+CD16++) monocytes in type 2 diabetes mellitus patients with/without chronic periodontitis. Dent Res J. 2019; 16(2): 95-103, CrossRef.

Nagasawa T, Kobayashi H, Aramaki M, Kiji M, Oda S, Izumi Y. Expression of CD14, CD16 and CD45RA on monocytes from periodontitis patients. J Periodontal Res. 2004; 39(1): 72-8, CrossRef.

Ziegler-Heitbrock L. The CD14+ CD16+ blood monocytes: their role in infection and inflammation. J Leukoc Biol. 2007; 81(3): 584-92, CrossRef.

Belge KU, Dayyani F, Horelt A, Siedlar M, Frankenberger M, Frankenberger B, et al. The proinflammatory CD14+CD16+DR++ monocytes are a major source of TNF. J Immunol. 2002; 168(7): 3536-42, CrossRef.

Vento-Tormo R, Company C, Rodríguez-Ubreva J, de la Rica L, Urquiza JM, Javierre BM, et al. IL-4 orchestrates STAT6-mediated DNA demethylation leading to dendritic cell differentiation. Genome Biol. 2016; 17: 4, CrossRef.

Goudot C, Coillard A, Villani AC, Gueguen P, Cros A, Sarkizova S, et al. Aryl hydrocarbon receptor controls monocyte differentiation into dendritic cells versus macrophages. Immunity. 2017; 47(3): 582-96.e6, CrossRef.

Zigmond E, Varol C, Farache J, Elmaliah E, Satpathy AT, Friedlander G, et al. Ly6C hi monocytes in the inflamed colon give rise to proinflammatory effector cells and migratory antigen-presenting cells. Immunity. 2012; 37(6): 1076-90, CrossRef.

Yu XH, Fu YC, Zhang DW, Yin K, Tang CK. Foam cells in atherosclerosis. Clin Chim Acta. 2013; 424: 245-52, CrossRef.

Nambo-Venegas R, Palacios-González B, Mas-Oliva J, Aurioles-Amozurrutia AK, Cruz-Rangel A, Moreno A, et al. Conversion of M1 macrophages to foam cells: Transcriptome differences determined by sex. Biomedicines. 2023; 11(2): 490, CrossRef.

Jagannathan R, Lavu V, Rao SR. Comparison of the proportion of non-classic (CD14+CD16+) monocytes/macrophages in peripheral blood and gingiva of healthy individuals and patients with chronic periodontitis. J Periodontol. 2014; 85(6): 852-8, CrossRef.

Valtierra-Alvarado MA, Castañeda Delgado JE, Ramírez-Talavera SI, Lugo-Villarino G, Dueñas-Arteaga F, Lugo-Sánchez A, et al. Type 2 diabetes mellitus metabolic control correlates with the phenotype of human monocytes and monocyte-derived macrophages. J Diabetes Complications. 2020; 34(11): 107708, CrossRef.

Hadadi E, Zhang B, Baidžajevas K, Yusof N, Puan KJ, Ong SM, et al. Differential IL-1β secretion by monocyte subsets is regulated by Hsp27 through modulating mRNA stability. Sci Rep. 2016; 6: 39035, CrossRef.

Gustine JN, Jones D. Immunopathology of hyperinflammation in COVID-19. Am J Pathol. 2021; 191(1): 4-17, CrossRef.

Chang SF, Chang PY, Chou YC, Lu SC. Electronegative LDL induces M1 polarization of human macrophages through a LOX-1-dependent pathway. Inflammation. 2020; 43(4): 1524-35, CrossRef.

Conget I, Giménez M. Glucose control and cardiovascular disease: Is it important? No. Diabetes Care. 2009; 32(Suppl 2): S334-6, CrossRef.

Teraguchi I, Imanishi T, Ozaki Y, Tanimoto T, Orii M, Shiono Y, et al. Impact of glucose fluctuation and monocyte subsets on coronary plaque rupture. Nutr Metab Cardiovasc Dis. 2014; 24(3): 309-14, CrossRef.

Min D, Brooks B, Wong J, Salomon R, Bao W, Harrisberg B, et al. Alterations in monocyte CD16 in association with diabetes complications. Mediators Inflamm. 2012: 2012: 649083, CrossRef.




DOI: https://doi.org/10.18585/inabj.v16i1.2798

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