Monocyte Expression of the Haemoglobin Scavenger Receptor CD163: Possible Role in the Development of Diabetes Complications — ASN Events
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  3. Monocyte Expression of the Haemoglobin Scavenger Receptor CD163: Possible Role in the Development of Diabetes Complications

Monocyte Expression of the Haemoglobin Scavenger Receptor CD163: Possible Role in the Development of Diabetes Complications (#92)

Danqing Min 1 2 , Sarah E. Aamidor 2 , Belinda A. Brooks 3 4 , Jencia Wong 2 3 , Linda A. Ban 2 , Brian Harrisberg 5 , Stephen M. Twigg 1 2 3 , Dennis K. Yue 1 2 3 , Susan V. 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

Our studies have shown that monocyte phenotypes are altered in association with diabetic complications status. CD163 is a marker of monocyte/macrophage function, and circulating CD163 (sCD163) is considered to be a marker of monocyte/macrophage activation. The relationship between cell surface CD163, sCD163 and proteinases such as MMP-9 (matrix metalloproteinase-9), known to be involved in its shedding, and diabetic complications has not been studied. In this study we examined the association between CD163 expression, sCD163 and diabetes complications presence in humans. Additionally the temporal relationship between these changes and kidney complications development was examined in mice.

For the human studies, blood was obtained from 43 diabetic patients with duration of diabetes>10 years (18 with and 25 without complications) and 22 non-diabetic controls. In mice, samples were obtained 5, 10 and 20 weeks after induction of diabetes with age matched non-diabetic mice as control (n=5-7/group). The CD163+ monocyte (%) was determined by flow cytometry, sCD163 by ELISA, CD163 gene expression by qRT-PCR and MMP-9 by zymography.

In humans, there was no difference in %CD163+ monocytes between control and diabetic subjects (median (IQR): 6.1(1.8-50.6) and 4.5(0.7-64.8) % respectively). However, for the diabetic cohort with complications, the %CD163+ monocytes were decreased while sCD163 level was increased (both P<0.05). The CD163 mRNA level and MMP-9 levels were not affected by diabetes or complications status. In diabetic mice, increased sCD163 at 5 weeks preceded decreased %CD163+ monocytes at week 10, and increased kidney collagen IV mRNA at week 20 (all P<0.05).

The higher sCD163 and decreased %CD163+ in diabetes is consistent with increased monocyte activation and shedding. Interestingly our inbred mouse data suggests that these changes precede the development of complications. Moreover the observation these changes are not observed in those patients who do not develop complications suggests a protective monocyte phenotype in this patient subgroup.

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