Functional characterization of monoclonal antibody inhibitors of α2- antiplasmin that accelerate fibrinolysis in different animal plasmas

Guy L. Reed

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

In humans with acute thrombotic disease, thrombi often appear to resist fibrinolysis induced by plasminogen activators. To examine the potential role of α2-antiplasmin (α2AP) in thrombus resistance in vivo, we generated monoclonal antibody inhibitors of α2AP. In a somatic cell fusion, 99 hybridomas were obtained that produced MAbs that bound to human 125I- α2AP in a capture assay. Screening assays showed that 3 of these MAbs, 49, 70, and 77, neutralized the function of α2AP. Immunoblotting experiments indicated that these MAbs recognized an epitope present in native α2AP that was destroyed by denaturation with SDS. Each of these MAbs fully inhibited the binding of the other MAbs to α2AP, but none of them competed with the binding of another anti-α2AP MAb, RWR. When tested for their binding to nonhuman α2APs in plasmas, all three MAbs were strongly crossreactive with all primate plasmas tested but showed an idiosyncratic pattern of binding to α2AP in other plasmas, suggesting unique fine epitope specificities. In human plasma, all three MAbs amplified the lysis of human plasma clots induced by plasminogen activators, increasing the potency of urokinase by nearly 50- to 100-fold. These MAbs also markedly amplified the lysis of clots from baboon, cynomolgus, african green monkey plasmas, and to a lesser extent, ferret and dog. By virtue of their ability to potently inhibit α2AP in other animal plasmas, these MAbs should be useful for examining the role of α2AP in thrombus resistance to fibrinolysis in vivo.

Original languageEnglish (US)
Pages (from-to)281-286
Number of pages6
JournalHybridoma
Volume16
Issue number3
DOIs
StatePublished - Jan 1 1997

Fingerprint

Antifibrinolytic Agents
Fibrinolysis
Monoclonal Antibodies
Thrombosis
Plasminogen Activators
Epitopes
Cercopithecus aethiops
Ferrets
Cell Fusion
Papio
Urokinase-Type Plasminogen Activator
Hybridomas
Acute Disease
Immunoblotting
Primates
Dogs

All Science Journal Classification (ASJC) codes

  • Immunology
  • Genetics

Cite this

Functional characterization of monoclonal antibody inhibitors of α2- antiplasmin that accelerate fibrinolysis in different animal plasmas. / Reed, Guy L.

In: Hybridoma, Vol. 16, No. 3, 01.01.1997, p. 281-286.

Research output: Contribution to journalArticle

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