The scavenger receptor CD163 is exclusively expressed by monocyte/macrophages and is shed by matrix metalloproteinases (MMPs) and neutrophil elastase (ELA2) as soluble CD163 (sCD163). Monocyte phenotype is altered in diabetes, but the relationship among monocyte CD163, sCD163, and diabetic complications is not known and was investigated in this study. Blood was obtained from patients with diabetes for >10 yr and mice with diabetes for ≤20 wk. Blood from people and mice without diabetes acted as controls. The percentage of CD163⁺ monocytes and monocyte CD163 mRNA was determined by flow cytometry and qRT-PCR, respectively. Plasma sCD163, MMPs, and ELA2 were measured by ELISA. The ability of glucocorticoids to stimulate isolated monocyte CD163 expression was also investigated. The percentage of CD163⁺ monocytes was significantly decreased and sCD163 significantly increased (both P < 0.05) in patients with diabetes with complications compared to those without complications. Plasma ELA2 and MMP-3 were also increased (P < 0.05), but CD163 mRNA was unaltered. sCD163 correlated with worsening renal function, as determined by eGFR (r = -0.48, P < 0.05). In diabetic mice, increased sCD163 at wk 5 and decreased percentage of CD163⁺ monocytes at wk 10 preceded alteration in kidney collagen IV mRNA at wk 20 (all P < 0.05). In vitro incubation of monocytes in anti-inflammatory glucocorticoid increased the percentage of CD163⁺ monocytes (P < 0.05). In people, higher sCD163 and decreased percentage of CD163⁺ monocytes were consistent with increased monocyte activation and shedding. The murine data indicated that these changes preceded the development of diabetic complications. Taken together, these results suggest that higher circulating percentage of CD163⁺ monocytes may have anti-inflammatory effects and may protect from development of diabetic complications.

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