ABERRANT NEUTROPHIL TRAFFICKING AND METABOLIC OSCILLATIONS IN SEVERE PYODERMA-GANGRENOSUM

Having previously associated metabolic oscillations with cell locomoti on, we hypothesized that patients with abnormalities in neutrophil tra fficking may display aberrant intracellular oscillations. A pyoderma g angrenosum patient exhibiting aberrant leukocyte trafficking in vivo a nd skin ulceration without infection was identified. This patient's ne utrophils constitutively overexpressed and clustered the leukocyte int egrins CR3 and CR I and failed to display appropriate integrin-to-GPI receptor interactions. Increased levels of tyrosine phosphorylation we re observed. NAD(P)H oscillations, which are sinusoidal in normals, we re chaotic with multiple frequency components in this patient's neutro phils. Normal cell shape and sinusoidal NAD(P)H oscillations were rest ored by providing a pulsed electric field to drive metabolic oscillati ons and by temperature reduction. N-acetyl-D-glucosamine disrupted CR3 clusters and sinusoidal NAD(P)H oscillations returned. Anecdotal repo rts suggest that local hypothermia is clinically useful for this patie nt. These data define the first metabolic oscillation-associated disea se and suggest that pyoderma gangrenosum can be classified as a dynami cal disease at the cellular level.