Activation of plasma Hageman factor and kallikrein in ongoing allergic reactions in the skin.
Ten atopic subjects, sensitive to intradermal injection of less than or equal to 10 protein nitrogen units of ragweed or grass pollen antigen, underwent paired antigen and buffer skin chamber incubation over the base of denuded skin blisters. The chamber fluids were sampled over a 6-hr period for histamine and activated Hageman factor and plasma kallikrein which were complexed to C1 inhibitor. In 9 of 10 subjects significantly (p less than 0.01) increased histamine levels (74 +/- 11 ng/ml vs 1.5 +/- 0.55 ng/ml) and kallikrein-C1 inhibitor complexes (2.15 +/- 0.78 ng/ml/hr vs 0.51 +/- 0.09 ng/ml/hr, p less than 0.25) were detected at antigen sites compared with buffer sites, respectively. Increased levels of activated Hageman factor (ng/ml/hr) were detected at antigen sites (1.35 +/- 0.60) compared with buffer sites (0.11 +/- 0.05), (p less than 0.01), in 8 of 10 subjects. Whereas peak levels of histamine were obtained after 1 hr of challenge, both Hageman factor and kallikrein activation, as assessed by complex formation, tended to peak later from the 2nd to the 5th hr. This represents the first demonstration that cutaneous IgE-mediated allergic responses are associated with local activation of the intrinsic plasma coagulation-kinin pathways.
Atkins
P C
PC
University of Pennsylvania School of Medicine, Department of Medicine, Philadelphia 19104.
Miragliotta
G
G
Talbot
S F
SF
Zweiman
B
B
Kaplan
A P
AP
D000328:Adult; D000485:Allergens; D003174:Complement C1 Inactivator Proteins / Q000378:metabolism; D004789:Enzyme Activation; D005174:Factor XII / Q000502:physiology*; D005260:Female; D006632:Histamine / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000503:physiopathology*; D007074:Immunoglobulin G / Q000378:metabolism; D007610:Kallikreins / Q000502:physiology*; D008297:Male; D011058:Pollen / Q000276:immunology; D012867:Skin / Q000503:physiopathology*
D000485:Allergens; D003174:Complement C1 Inactivator Proteins; D007074:Immunoglobulin G; D006632:Histamine; D005174:Factor XII; D007610:Kallikreins