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Neutrophil activation is induced by wounding in diabetes (#246)

Maryam Abdollahi 1 , Taria Ng 1 , Sarah Aamidor 1 , Alireza Rezaeizadeh 1 , Stephen Twigg 1 2 , Danqing Min 1 2 , Susan McLennan 1 2
  1. Greg Brown Diabetes and Endocrinology Research Laboratory, Sydney Medical School, Charles Perkins Centre, Bosch Institute, University of Sydney, Sydney, NSW, Australia
  2. Dept of Endocrinology, RPA Hospital, Sydney, NSW, Australia

Diabetes is known to impair wound healing and neutrophil function but whether wounding affects circulating and wound neutrophil activation is not known. Therefore we examined the activation of circulating neutrophils before and after wounding in our rodent diabetic wound model. The results were compared with those obtained from wound neutrophils. The effect of insulin treatment was also investigated.

For these studies age matched control (CON), diabetic (DM), and insulin treated diabetic (D+INS:10IU/day) rats were studied (n=6-10/group). Six weeks later some animals were anesthetised and PVC sponges (4x1cm2) were placed in the flanks. CON and DM animals not implanted with sponges acted as unwounded controls. After 6 days all animals were sacrificed and blood was obtained for neutrophil isolation and the fluids and infiltrated cells were isolated from the sponges. Neutrophil specific marker (MMP-8) and markers increased with neutrophil activation (NGAL and MMP-9) were measured in circulating neutrophils and sponge cells by qRT-PCR. Circulating neutrophil number was determined by flow cytometry and Mcl-1 an anti-apoptotic marker was studied by qRT-PCR. In unwounded animals, diabetes had no effect on circulating neutrophil number, activation and Mcl-1 expression. In contrast in wounded animals, diabetes significantly increased circulating neutrophil number, NGAL, MMP-8, MMP-9 and Mcl-1, all greater than 2.5 fold and each P<0.05 compared with control. In sponge cells diabetes increased neutrophil number, MMP-8 and NGAL (by >1.8 fold, P<0.05) but MMP-9 was unaltered. Insulin treatment from the onset of diabetes normalised the effects of diabetes and wounding.

Wounding of diabetic animals increased circulating and sponge neutrophil number and activation and decreased apoptosis.  Whilst whether apoptosis is dysregulated is unclear the observed increase in Mcl-1 suggests increased neutrophil longevity. Together these changes are proinflammatory. That insulin treatment can prevent these changes, suggests that glycemic control is likely an important protective factor. Supported by IPRS, APA, NH&MRC