Change in Circulating Monocyte Profile with Foot Ulcer Healing in Diabetic Patients

Poor wound healing in diabetes is associated with increased chronic inflammation and alterations in macrophage accumulation. Chronic inflammation can alter the phenotype of macrophage precursors, monocytes but whether their phenotype is changed in association with wound healing is not known. Blood was obtained from 21 patients (14 male: 7 female) attending the High Risk Foot Clinic at RPA Hospital at their initial visit (V1), week 4 (V2) and week 8 (V3). Wound area was measured and wound type was assessed by a podiatrist. Monocyte number (CD14 + ), phenotype as classical (CD16 − ), non-classical (CD16 ++ ), and intermediate (CD16 + ), anti-inflammatory (CD163 + ) subset and expression of receptors CCR2, CCR5 and TLR2, TLR4 were determined by flow cytometry. The MMPs and TIMP-1 were measured in plasma by zymography and ELISA. Over the 8 weeks, 6 ulcers healed (H) and 15 failed to heal (NH). The age, duration of diabetes, HbA1c, wound size and duration at V1 were not different between the groups but the % CD16 ++ monocytes was higher in H vs. NH at V1 (23.5 vs. 8.3) and V3 (17.4 vs. 7.2) and monocyte CCR2 + was lower in H at V3 (P ++ (r=0.42), CD16 + (r=0.39), CD163 + (r=0.37), and CD14 + (r=-0.39), CD16 - (r=-0.52), as well as plasma MMP-2 (r=-0.67) and MMP-9 (r=-0.41)(P ++ and CD16 - and plasma MMP-2 (P Disclosure D. Min: None. V.L. Nube: None. A. Tao: None. X. Yuan: None. B. Brooks: None. J. Wong: Speaker9s Bureau; Self; Novo Nordisk A/S, AstraZeneca, Eli Lilly and Company. S.M. Twigg: Advisory Panel; Self; Abbott. Consultant; Self; Abbott. Advisory Panel; Self; Novo Nordisk Inc., Sanofi-Aventis, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company. Speaker9s Bureau; Self; AstraZeneca, Merck Sharp & Dohme Corp.. Other Relationship; Self; Abbott. S. McLennan: None.