To investigate the regional viscoelasticity of locomoting neutrophils in a patient with Job’s syndrome, in both a stable condition and in a condition with severe infection.
We measured regional rheological properties in the leading, body, and trailing regions of spontaneously locomoting neutrophils in a patient with Job’s syndrome (27yo, male) in a stable condition and in a condition with pneumonia and meningitis, and compared the results with those of normal subjects. We optically trapped intracellular granules and measured their displacement for 500ms following a 100nm step change in the trap position. Results were analyzed in terms of a simple viscoelasticity model, and using the structural damping model (stress relaxation follows a power law in time).
Regional viscoelastic stiffness and viscosity or structural damping storage and loss moduli were all significantly lower in leading regions compared to pooled body/trailing regions (the latter were not significantly different); leading regions were significantly more fluid-like than body/trailing regions in both the patient and normals. The rheology of leading region and body/trailing regions of neutrophils in the stable patient is ∼50% less elastic and less viscous than that in normals. Neutrophils obtained when the patient suffered from pneumonia and meningitis were not significantly different rheologically from those obtained when the patient was in a stable condition.
1) The significantly more fluid-like behavior of the leading edge supports the idea that intracellular pressure may be the origin of motive force in neutrophil locomotion. 2) In a patient with Job’s syndrome, neutrophils are less viscoelastic than those in normals. Moreover, neutrophils failed to show any significant stiffening when the patient suffered from severe infection. These results may account in part for neutrophil dysfunction in Job’s syndrome.
Intervention to make neutrophils stiffer may be helpful in improving neutrophil function in patients with Job’s syndrome.
Masaru Yanai, Grant monies (from sources other than industry) From the Ministry of Education and Science, Japan.