Heparin, derived from the mast cells of human lungs is responsible for the generation of kinins in allergic reactions due to the activation of the contact system.
BACKGROUND
In a recent study mast cell heparin proteoglycan (HepPG) of a cell line derived from a mouse mastocytoma was isolated. Glycosaminoglycans proved to be an initiating surface for starting contact activation and could explain kinin generation present in allergic reactions. It is the aim of the present study to prove that HepPG or glycosaminoglycan derived from human mast cells is also capable of acting as a physiologic macromolecule and to induce contact activation.


METHODS
HepPG molecules were isolated by anionic column chromatography. Their ability to accelerate reciprocal activation of factor XII was investigated by spectrophotometry. The anticoagulant effect was demonstrated by an increase in partial thromboplastin time. HPLC was performed to correlate these effects with molecular weight (MW).


RESULTS
The isolated heparin showed high contact-activating and anticoagulant potency. Both actions were suppressed by incubation with heparinase I. The maximum contact activation peak appeared at a lower MW than the anticoagulant effect.


CONCLUSIONS
These in vitro results explain the results of in vivo allergen challenge studies where a high degree of kinin generation occurs. Heparin derived from human mast cells therefore seems to represent the physiological macromolecule capable of activating the contact system and could be a missing link between cellular and humoral responses in allergic reactions.
Noga
O
O
Allergy and Asthma Clinic, Humboldt University Berlin, Virchow Klinikum, Berlin, Germany.
Brunnée
T
T
Schäper
C
C
Kunkel
G
G
D000818:Animals; D002850:Chromatography, Gel; D003877:Dermatitis, Contact / Q000209:etiology / Q000276:immunology*; D004789:Enzyme Activation; D006493:Heparin / Q000031:analogs & derivatives / Q000276:immunology / Q000302:isolation & purification; D019763:Heparin Lyase / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism*; D018836:Inflammation Mediators / Q000276:immunology / Q000302:isolation & purification; D007705:Kinins / Q000096:biosynthesis; D008168:Lung / Q000166:cytology*; D008407:Mast Cells / Q000737:chemistry*; D011509:Proteoglycans / Q000276:immunology / Q000302:isolation & purification
D018836:Inflammation Mediators; D007705:Kinins; D011509:Proteoglycans; C036090:heparin proteoglycan; D006493:Heparin; D019763:Heparin Lyase