Platelet-activating factor induces histamine release from human skin mast cells in vivo, which is reduced by local nerve blockade.
BACKGROUND
Intradermal injection of platelet-activating factor (PAF) causes wheal and flare reactions, which are inhibited by antihistamines. However, PAF does not release histamine from human dispersed skin mast cells in vitro. The purpose of this study was to investigate the extent and possible mechanisms of PAF-induced histamine release in human skin in vivo with the use of dermal microdialysis.


METHODS
Hollow dialysis fibers were inserted into the upper dermis in forearm skin and each fiber was perfused with Krebs-Ringer bicarbonate solution at a rate of 3.0 microliters/min. PAF (4.5 to 36 mumol/L), lyso-PAF (36 mumol/L), vehicle (negative control), and codeine 750 or 250 mumol/L (positive control) were injected intradermally above separate fibers. Dialysate was collected in 2-minute fractions for 20 minutes and histamine analyzed spectrofluorometrically.


RESULTS
PAF, but not lyso-PAF, caused statistically significant dose-related histamine release and wheal and flare reactions. Intradermal mepivacaine administration significantly abrogated flare reactions by PAF and codeine and inhibited histamine release and wheal reactions by PAF but not by codeine. Long-term topical capsaicin administration inhibited histamine release and wheal reactions by PAF but not by codeine. It inhibited flare reactions induced by both compounds. PAF did not release histamine from blood basophils.


CONCLUSIONS
These data suggest that PAF induced histamine release from mast cells in intact human skin indirectly via neurogenic activation. Further, on the intradermal injection of PAF histamine release and the skin responses, the wheal and the flare, are differentially regulated by neurogenic components.
Petersen
L J
LJ
Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Denmark.
Church
M K
MK
Skov
P S
PS
D000328:Adult; D000779:Anesthetics, Local / Q000494:pharmacology*; D001491:Basophils / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006636:Histamine Release / Q000502:physiology*; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000187:drug effects*; D008619:Mepivacaine / Q000494:pharmacology; D017551:Microdialysis; D008875:Middle Aged; D009407:Nerve Block; D010972:Platelet Activating Factor / Q000494:pharmacology*; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000294:innervation
D000779:Anesthetics, Local; D010972:Platelet Activating Factor; D008619:Mepivacaine; D002211:Capsaicin