Monocyte Surface and Soluble Levels of the Haemoglobin Scavenger Receptor CD163: Possible Role in the Development of Diabetes Complications — ASN Events
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  3. Monocyte Surface and Soluble Levels of the Haemoglobin Scavenger Receptor CD163: Possible Role in the Development of Diabetes Complications

Monocyte Surface and Soluble Levels of the Haemoglobin Scavenger Receptor CD163: Possible Role in the Development of Diabetes Complications (#86)

Danqing Min 1 2 , Jencia Wong 1 2 3 , Belinda Brooks 3 4 , Sarah Aamidor 2 , Christine Yee 2 , Brian Harrisberg 5 , Stephen Twigg 1 2 3 , Dennis Yue 1 2 3 , Susan McLennan 1 2
  1. Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
  2. Greg Brown Diabetes and Endocrinology Research Laboratory, Sydney Medical School, Charles Perkins Centre, Bosch Institute, University of Sydney, Sydney, NSW, Australia
  3. Diabetes Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia
  4. Sydney Nursing School, University of Sydney, Sydney, NSW, Australia
  5. Department of Ophthalmology, Royal Prince Alfred Hospital, Sydney, NSW, Australia

We have previously shown that monocyte phenotype is altered in association with diabetes complications status. CD163 is a haemoglobin scavenger receptor exclusively expressed on the cell surface of monocytes/macrophages. CD163 plays an anti-inflammatory role and circulating soluble CD163 (sCD163) is a marker of monocyte/macrophage activation. The relationship between CD163, proteinases such as matrix metalloproteinases (MMPs) and neutrophil elastase (ELA2) involved in CD163 shedding and diabetes complications has not been studied and was examined in this study in humans. Furthermore a diabetic mouse model was used to investigate the temporal changes in CD163 during development of complications.

In humans, blood was obtained from control and diabetic patients with or without complications despite a long duration of diabetes >10 years. In mice, blood was obtained from control and diabetic mice after 5, 10 and 20 weeks of diabetes. Monocyte CD163+ (%) and CD163 gene expression were determined by flow cytometry and qRT-PCR respectively. sCD163, MMP-3 and TIMP-1 were measured in plasma by ELISA and MMP-2 by zymography.

In humans, diabetes was associated with decreased %CD163+ monocytes and increased sCD163, but only in those with complications (by 16 and 1.6 fold respectively, both P<0.05). Circulating MMP-3 and ELA2 were also increased in those with complications (each P<0.05). The expression of MMP-2 and MMP-2/TIMP-1 ratio was increased in diabetes irrespective of complications status. In mice, diabetes increased sCD163 at 5 weeks which preceded decreased %CD163+ monocytes at 10 weeks, and increased kidney collagen IV at 20 weeks.

The higher sCD163 and decreased %CD163+ in diabetes is consistent with increased monocyte activation and shedding. Our mouse data suggests that higher sCD163 and decreased monocyte %CD163+ precedes development of diabetes complications which may have utility as an early biomarker of complications risk.  Moreover the observation that these changes are not observed in those patients who remain complications free after a long duration of diabetes suggests a protective monocyte phenotype in this subgroup of patients.

Supported by Diabetes Australia Research Trust.