title: D-dimer specific monoclonal antibodies react with fibrinogen aggregates.
abstract: Human fibrinogen exposed to 46.5 degrees C was subjected to gel permeation chromatography. The protein eluted in two distinct peaks. The first peak appeared in the void volume containing soluble fibrinogen aggregates, while the other peak represented monomeric fibrinogen. In contrast to the monomeric peak material, the aggregate fraction reacted with a panel of monoclonal antibodies specific for fragment D-dimer using an ELISA system. Edman degradation showed that both the aggregate and the monomeric fractions were devoid of soluble fibrin, and immunoblots of SDS-PAG electrophoretic profiles disclosed no sign of stabilized high molecular weight derivatives. We have previously shown that the aggregate fraction of similarly treated fibrinogen, in contrast to the monomeric fraction, stimulates the t-PA catalyzed conversion of plasminogen to plasmin and concomitantly exposes the sequences Aalpha-(148-160) and gamma-(312-324) involved in t-PA stimulation. Our present and previous findings suggest that soluble fibrinogen aggregates possess a fibrin-like structure, and that fibrin or fibrinogen polymer formation is a prerequisite for the enhancing effect on t-PA-mediated plasminogen to plasmin conversion which is seen even with the polymers in the soluble state.
authors.affiliation: Research Institute for Internal Medicine, Rikshospitalet, Oslo, Norway.
authors.forename: A
authors.initials: A
authors.lastname: Bennick
authors.forename: U
authors.initials: U
authors.lastname: Haddeland
authors.forename: F
authors.initials: F
authors.lastname: Brosstad
mesh_terms: D000911:Antibodies, Monoclonal; D002850:Chromatography, Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005338:Fibrin Fibrinogen Degradation Products / Q000276:immunology*; D005340:Fibrinogen / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting
chemical_list: D000911:Antibodies, Monoclonal; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D005340:Fibrinogen