Are cysteinyl leukotrienes involved in allergic responses in human skin?
BACKGROUND
Cysteinyl leukotrienes have been suggested to be involved in producing the symptoms of both the early and late phases of the allergic response in the lung and other tissues.


OBJECTIVE
To use scanning laser Doppler imaging, microdialysis and immunocytochemistry to explore the mediator and cellular mechanisms of the dermal allergic response.


METHODS
Thirteen atopic volunteers received intradermal injections into the forearm of grass pollen or D. pteronyssinus extract. Changes in dermal blood flow up to 8 h were monitored by scanning laser Doppler imaging. The release of histamine, PGD2 and LTC4/D4/E4 was assessed by dermal microdialysis. Skin biopsies were taken at 6 h to determine numbers of mast cells, eosinophils, basophils, Langerhans' cells, and monocytes/macrophages, and the expression of COX-1, COX-2, 5-LO and FLAP.


RESULTS
Allergen provocation produced an immediate weal and flare response followed by an erythematous induration peaking at 6 h. During the first hour, c. 84 pmoles of histamine and c. 0.3 pmoles of PGD2 were recovered by microdialysis (both P < 0.001) but LTC4/D4/E4 was undetectable. No histamine, PGD2 or LTC4/D4/E4 was detectable at later times. Immunocytochemical examination of biopsies taken at 8 h showed increased numbers of eosinophils and basophils and in COX-2, 5-LO and FLAP, but not COX-1. Expression of 5-LO and FLAP was associated primarily with eosinophils.


CONCLUSIONS
These findings suggest that inflammatory cells recruited to the site of allergen injection are not activated to release detectable amounts of cysteinyl leukotrienes. Hence, it is unlikely that the late-phase erythematous induration is mediated by this autocoid.
Church
M K
MK
Division of Infection, Inflammation and Repair, School of Medicine, University of Southampton, Southampton, UK. mkc@soton.ac.uk
Griffiths
T J
TJ
Jeffery
S
S
Ravell
L C
LC
Cowburn
A S
AS
Sampson
A P
AP
Clough
G F
GF
D058927:5-Lipoxygenase-Activating Proteins; D000328:Adult; D001094:Arachidonate 5-Lipoxygenase / Q000032:analysis; D001706:Biopsy; D002352:Carrier Proteins / Q000032:analysis; D003545:Cysteine / Q000502:physiology*; D005260:Female; D006636:Histamine Release; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology*; D015289:Leukotrienes / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D012867:Skin / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D002352:Carrier Proteins; D015289:Leukotrienes; D008565:Membrane Proteins; C112381:cysteinyl-leukotriene; D001094:Arachidonate 5-Lipoxygenase; D003545:Cysteine