Extracellular deposition of eosinophil and neutrophil granule proteins in the IgE-mediated cutaneous late phase reaction.
Intradermal injection of allergens in sensitive subjects produces an IgE-dependent prolonged inflammatory reaction, the late phase reaction (LPR). Histologically, eosinophils are present in the LPR but are not as numerous as neutrophils or mononuclear cells. We determined whether extracellular deposition of eosinophil and neutrophil granule proteins occurs in the LPR by immunofluorescent localization of eosinophil granule major basic protein (MBP), eosinophil-derived neurotoxin (EDN), and neutrophil elastase. Before intradermal challenge, eosinophils and neutrophils were present only in blood vessels, and MBP, EDN, and elastase were localized to cells. At 15 minutes, small amounts of MBP, EDN and elastase were found outside of cells in focal areas. By 1 to 3 hours, MBP, EDN and elastase were extensively deposited throughout the dermis in a granular and diffuse manner; these deposits persisted up to 56 hours. Both actively and passively sensitized subjects showed similar MBP and elastase deposition. Skin sites passively sensitized by sera depleted of IgE showed essentially no MBP or elastase deposition. Electron microscopy showed degenerating eosinophils and free eosinophil granules in the dermis. Mast cell numbers diminished during the LPR when extracellular eosinophil and neutrophil granule protein deposition was maximal. These results demonstrate that striking dermal eosinophil and neutrophil granule protein deposits are prominent features of the cutaneous LPR, are IgE-dependent and precede the maximal clinical expression of the LPR. The possible significance of these findings in the pathophysiology of the LPR is discussed.
Department of Dermatology, Mayo Clinic, Rochester, Minnesota.
K M
KM
Leiferman
T
T
Fujisawa
B H
BH
Gray
G J
GJ
Gleich
D000279:Administration, Cutaneous; D001798:Blood Proteins / Q000378:metabolism*; D002452:Cell Count; D047091:Eosinophil Granule Proteins; D047208:Eosinophil-Derived Neurotoxin; D004804:Eosinophils / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology* / Q000378:metabolism; D007073:Immunoglobulin E / Q000502:physiology*; D008407:Mast Cells / Q000276:immunology; D008854:Microscopy, Electron; D009498:Neurotoxins / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000378:metabolism*; D012260:Ribonucleases; D012867:Skin / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D009498:Neurotoxins; D007073:Immunoglobulin E; D047208:Eosinophil-Derived Neurotoxin; D012260:Ribonucleases; D010196:Pancreatic Elastase