An active fraction of unfractionated heparin from a natural source is recognized by the first component of the complement system.
Heparin is a natural glycosaminoglycan with chains consisting of alternating 1-4 linked residues of sulphated uronic acids (L-iduronic in great proportion) and D- glucosamine attached to a serine-glycine linear protein core. In our previous experiments with a low molecular weight heparin (Mr = 4.000 to 6.000) obtained by partial chemical degradation of the original heparin we could concentrate its anticoagulant activity by precipitation with the first component of the human complement system. In order to confirm these results with a more physiological unfractionated heparin we used commercial heparin from porcine intestinal mucose with a high molecular weight (9.000-15.000) and a specific activity of 179 U/mg. An heparin fraction with high anticoagulant activity was isolated from the precipitate of the interaction between this high molecular weight heparin isolated from a natural source, and the first component of the human complement system. Our results confirmed, in opposition to almost all early literature, that under very strict conditions of pH 6.0, calcium chloride concentration (2 mM), and very low ionic strength (25 mM), the first component of the human complement cascade recognize heparin fractions "enriched" in the high affinity sequence for the antithrombin III.
Calabrese
G C
GC
Departamento de Ciencias Biológicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Leocatanieto
F
F
Recondo
E F
EF
Fernandez de Recondo
M E
ME
D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003172:Complement C1 / Q000378:metabolism*; D006493:Heparin / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000737:chemistry; D008970:Molecular Weight; D013552:Swine
D003172:Complement C1; D000990:Antithrombin III; D006493:Heparin; D002118:Calcium