Altered rheology of lymphocytes in the diabetic mouse

Abstract

Aims/hypothesis. Clinical complications associated with diabetes may be related to altered physical properties of leucocytes. We used micropipette techniques to examine leucocyte rheology (specifically lymphocyte rheology) in the non-obese diabetic (NOD) mouse model of diabetes mellitus. We hypothesised that diabetes affects lymphocyte rheology, and specifically that lymphocyte membranes from diabetic mammals have a higher cortical tension than those from non-diabetic mammals. Methods. Lymphocytes were isolated from diabetic and control mice. Lymphocyte deformation and activation were assessed with a micropipette apparatus. Cellular activation was assessed visually. Projection length into the micropipette during aspiration was used to calculate the viscosity of the cell. Recovery length following expulsion from the micropipette was used to derive the recovery time constant, which is the ratio of cortical tension : viscosity (To/μ) for each cell. The cell cortical/surface tension was calculated from this ratio. Results. Of 692 control lymphocytes, 29% were spontaneously activated compared with 39% of 624 diabetic cells (p<0.06) and 31.5% of 315 non-diabetic NOD cells (p=0.14). Viscosity values for diabetic lymphocytes were equivalent to those for control cells (1345.12±1420.97 Pa.s vs 996.84±585.07 Pa.s, p=0.13). The average To/μ value for diabetic lymphocytes (35.4±16. 5×10-6 cm/s) was significantly higher than that for control cells (24.8±11.3×10-6 cm/s, p<0.03) and cells from non-diabetic NOD mice (26.3± 9.0×10-6 cm/s, p<0.005). The mean cortical tension values for diabetic and control cells were 4.7± 2.3×10-4 N/m and 2.8±0.7×10 -4 N/m respectively (p<0.003). Conclusions/interpretation. Lymphocytes from diabetic mice tend to spontaneously activate. They have an equivalent cytoplasmic viscosity but a larger recovery time constant compared with cells from control mice. The results suggest that diabetic lymphocytes are stiffer than control cells.