Human Fibrinogen Heterogeneities

Abstract

Abstract The two types of human fibrinogen (Peaks 1 and 2) distinguishable by chromatography on DEAE-cellulose were isolated and the S-sulfo derivatives of the constituent Aα, Bβ, and γ chains separated and examined. No differences were found between the Aα and Bβ chains of Peak 1 fibrinogen and the corresponding chains of Peak 2 fibrinogen with respect to their chromatographic elution profiles, electrophoretic migration at pH 8.6 or 2.7, molecular size, or tryptic peptide maps. By chromatography on CM-cellulose, the γ chains of both types of fibrinogen were resolved into two approximately equal populations, designated γ-I (first eluted) and γ-2. Upon electrophoresis at pH 8.6 or 2.7 both the γ-1 and γ-2 chains of Peak 1 fibrinogen migrated as a single band. The corresponding chromatographically isolated chains of Peak 2 fibrinogen separated into two bands, designated γ and γ'. The γ' chains, which were the more anodal, amounted to about half of the γ chain population of Peak 2 fibrinogen. The γ chains of Peak 2 fibrinogen exhibited the same mobility as the corresponding chains of Peak 1 fibrinogen. The γ:γ' heterogeneity accounts for the charge difference between unmodified Peak 1 and Peak 2 fibrinogen. As assessed by electrophoretic experiments in the presence of sodium dodecyl sulfate after reduction of disulfide bonds, all γ chain variants were of the same molecular size and were capable of covalent cross-linking.