Interactions of eosinophil granule proteins with skin: limits of detection, persistence, and vasopermeabilization.
BACKGROUND
Eosinophil granule proteins, including eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), eosinophil peroxidase (EPO), and major basic protein (MBP), are prominently deposited in skin in several cutaneous disorders and likely contribute to disease pathology.


OBJECTIVE
We sought to determine the limit of detection, persistence, and vasopermeabilization activity of the eosinophil granule proteins in skin.


METHODS
The eosinophil granule proteins were injected intradermally. Their minimum detectable concentrations in human surgical waste skin and their persistence in guinea pig skin were determined by indirect immunofluorescence. Vasopermeabilization activity in the guinea pig without and with H1 antihistamine (pyrilamine maleate) pretreatment was assessed by extrusion of Evans blue dye-treated plasma.


RESULTS
The lowest detectable cutaneous concentrations were 0.05 micromol/L EPO, 0.1 micromol/L MBP, 0.25 micromol/L ECP, and 1 micromol/L EDN. Granule proteins persisted in guinea pig skin in vivo for 1 week (EPO), 2 weeks (ECP), 2.5 weeks (EDN), and 6 weeks (MBP). Each of the eosinophil granule proteins increased cutaneous vasopermeability in a concentration-dependent manner. The potency of vasopermeabilization induced by each granule protein was comparable with that of histamine. Pyrilamine maleate pretreatment of guinea pigs did not alter increased vasopermeability induced by ECP and EDN but significantly inhibited that induced by EPO and MBP.


CONCLUSIONS
Micromolar concentrations of eosinophil granule proteins are often deposited in skin in eosinophil-associated cutaneous disorders such as atopic dermatitis. These pathophysiologically relevant concentrations of eosinophil granule proteins cause increased cutaneous vasopermeability (both by means of histamine-independent and histamine-dependent mechanisms) and might alter cutaneous function for days to weeks.
Davis
Mark D P
MD
Department of Dermatology, Mayo Clinic and Foundation, Rochester, Minn, USA.
Plager
Douglas A
DA
George
Terry J
TJ
Weiss
Ellen A
EA
Gleich
Gerald J
GJ
Leiferman
Kristin M
KM
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism* / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects; D047091:Eosinophil Granule Proteins; D047209:Eosinophil Peroxidase; D047208:Eosinophil-Derived Neurotoxin; D019084:Fluorescent Antibody Technique, Indirect; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006801:Humans; D009994:Osmolar Concentration; D010544:Peroxidases / Q000378:metabolism* / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D012260:Ribonucleases / Q000378:metabolism* / Q000494:pharmacology; D012867:Skin / Q000098:blood supply / Q000378:metabolism*; D013997:Time Factors
D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D006634:Histamine H1 Antagonists; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D047208:Eosinophil-Derived Neurotoxin; D012260:Ribonucleases; D011738:Pyrilamine