Heparin and modified heparin inhibit complement activation in vivo.
Heparin regulates C activity in vitro, but has not been examined for this activity in vivo. The present study investigated the ability of commercial heparin and derivatized (N-desulfated, N-acetylated) heparin (Hep-NAc) with greatly diminished anticoagulant activity to inhibit C activation in guinea pigs. Catheters were placed in the right atrium of guinea pigs and kept patent with frequent saline flushes. The next day, heparin, Hep-NAc, or saline was given and 2.5 min later cobra venom factor or saline was given. Blood was drawn at intervals and assayed for total hemolytic C, C3 hemolytic activity, free hemoglobin, and activated partial thromboplastin time. Total hemolytic C and C3 activity decreased less rapidly in heparin- and Hep-NAc-pretreated animals than in non-pretreated animals, indicating that both heparins inhibited C activation. Heparin and Hep-NAc also inhibited cobra venom factor-induced hemolysis. This study demonstrates that commercial heparin and modified heparin inhibit C activation in vivo. This represents an important step in the development of an oligosaccharide drug to regulate C activation.
Weiler
J M
JM
Iowa City Veterans Administration Medical Center, IA.
Edens
R E
RE
Linhardt
R J
RJ
Kapelanski
D P
DP
D000818:Animals; D003167:Complement Activation / Q000187:drug effects*; D003176:Complement C3 / Q000378:metabolism; D015941:Complement Hemolytic Activity Assay; D004546:Elapid Venoms / Q000494:pharmacology; D006168:Guinea Pigs; D006493:Heparin / Q000494:pharmacology*; D008297:Male; D010314:Partial Thromboplastin Time
D003176:Complement C3; D004546:Elapid Venoms; C016310:cobra venom factor; D006493:Heparin