Alterations in macrophage accumulation and function play a role in poor wound healing in diabetes but whether the profile of their precursor, the monocyte, is changed as the wound heals is not known and was investigated in this study.
Blood was obtained from 15 patients attending the High Risk Foot Clinic at RPA Hospital at their initial visit (V1), week 4 (V2) and week 8 (V3) or when the ulcer healed (V3). Wound area was measured and wound type was assessed by the podiatrist and staged using the Texas system. Monocyte number (% CD14+), phenotype (% CD16+) and their expression of cell surface receptors CCR2, CCR5, TLR2 and TLR4 were determined by flow cytometry. At the V1, 12/15 ulcers were infected and 3/15 were both ischemic and infected. Over the study period 3 ulcers (all non-ischemic) healed completely and wound area decreased by 77.2±41.9%. At V1 the % CD14+ monocyte and %CCR2+, %CCR5+ and %TLR4+ monocytes were not different but %TLR2+ tended to be lower in those with infection and ischemia. Irrespective of wound grade, between V1 and V3 the %CD14+and %CD14+CD16- monocytes decreased (both by 2 fold, P<0.05). This difference was even greater when the 3/15 Texas stage D ulcers were excluded (P<0.01). For all samples wound area correlated with the monocyte expression of CCR2 (r=0.36, P<0.05), CCR5 (r=0.47, P<0.01) and TLR4 (r=-0.36, P<0.05).
These results in diabetic patients with foot ulcers suggest that circulating monocyte number in particular those of the classical phenotype (CD14+CD16-) are altered as the wound heals. Together this decrease in monocytes of the classical phenotype and the positive correlation between their expression of CCR2 and CCR5 and wound area suggests decreased inflammation. The exact relationships of these markers with infection and ischemia, and impaired diabetic wound healing warrants further investigation.