Adachi Y, Kindzelskii AL, Cookingham G, Shaya S, Moore EC, Todd RF 3rd, Petty HR, et al.
The Journal of investigative dermatology. Date of publication 1998 Aug 1;volume 111(2):259-68.
1. J Invest Dermatol. 1998 Aug;111(2):259-68.
Aberrant neutrophil trafficking and metabolic oscillations in severe pyoderma
gangrenosum.
Adachi Y(1), Kindzelskii AL, Cookingham G, Shaya S, Moore EC, Todd RF 3rd, Petty
HR.
Author information:
(1)Department of Biological Sciences, Wayne State University, Detroit, Michigan
48202, USA.
Having previously associated metabolic oscillations with cell locomotion, we
hypothesized that patients with abnormalities in neutrophil trafficking may
display aberrant intracellular oscillations. A pyoderma gangrenosum patient
exhibiting aberrant leukocyte trafficking in vivo and skin ulceration without
infection was identified. This patient's neutrophils constitutively overexpressed
and clustered the leukocyte integrins CR3 and CR4 and failed to display
appropriate integrin-to-GPI receptor interactions. Increased levels of tyrosine
phosphorylation were observed. NAD(P)H oscillations, which are sinusoidal in
normals, were chaotic with multiple frequency components in this patient's
neutrophils. Normal cell shape and sinusoidal NAD(P)H oscillations were restored
by providing a pulsed electric field to drive metabolic oscillations and by
temperature reduction. N-acetyl-D-glucosamine disrupted CR3 clusters and
sinusoidal NAD(P)H oscillations returned. Anecdotal reports suggest that local
hypothermia is clinically useful for this patient. These data define the first
metabolic oscillation-associated disease and suggest that pyoderma gangrenosum
can be classified as a dynamical disease at the cellular level.
DOI: 10.1046/j.1523-1747.1998.00311.x
PMID: 9699727 [Indexed for MEDLINE]
