Alterations in circulating CD16<sup>+</sup> neutrophils association with diabetes complications — ASN Events

Alterations in circulating CD16+ neutrophils association with diabetes complications (#230)

Danqing Min 1 2 , Belinda Brooks 3 4 , Jencia Wong 2 3 , Robert Salomon 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

Neutrophils play an essential role in immune defence and their function is altered in diabetes [1]. They are short lived in the circulation and the tissue and whilst neutrophils undergo apoptosis they lose function and the expression of the cell surface marker CD16 (FcγRIIIb) [2]. Whether diabetes affects neutrophil CD16 expression and its relationship with complications status is not known and was investigated in this study. Blood was obtained from 22 non-diabetic controls and 43 diabetic subjects who had duration of diabetes > 10 years and included 25 without and 18 with diabetic complications. In each subject the number of neutrophils, identified by cell surface markers CD45+CD14-CD11b+, neutrophil viability and CD16+ neutrophils were determined by flow cytometry. Clinical data were collected and the neutrophil specific matrix metalloproteinase-8 (MMP-8) was measured by ELISA. Diabetes decreased the viable neutrophil number as well as the CD16+ neutrophil population (2.5 and 1.8 fold respectively, each P<0.05) but the total neutrophil number was not altered. Within the diabetic group the percentage of CD16+ neutrophils was decreased in those with complications compared to those without (by 2 fold, P<0.05) but neutrophil viability was not altered. Within the diabetic subjects, the expression of MMP-8 was not changed but it was correlated with the percentage of CD16+ neutrophils (r=0.4, P= 0.005). These results suggest that in addition to effects on neutrophil function, diabetes and its complications also affect neutrophil viability and apoptosis detected by CD16 expression. The association between neutrophil CD16 and MMP-8 also suggests loss of neutrophil function. A reduction in neutrophil viability and function may result in a failure of induction of other immune cells and an altered local immune response. As neutrophils are a critical first line defence, understanding the relationships between these changes may provide valuable new insights into the pathogenesis of diabetic complications.

[1]. Alba-Loureiro, T.C. et al., Brazilian Journal of Medical and Biological Research (2007) 40: 1037-1044.

[2]. Dransfield, I. et al., J Immunol. (1994) 153(3): 1254-63.