| Abstrakt: |
Human fibrinogen interacts with pathogenic staphylococci, causing their clumping through an unexplained mechanism. We attempted to characterize the interaction between the staphylococcal fibrinogen receptor(s) and the binding region on the fibrinogen molecule by employing binding studies and the clumping reaction. Binding studies revealed that the Aα chain of human fibrinogen possesses a high affinity for staphylococci, the affinity of the Bβ chain is somewhat less, and the γ chain has no apparent affinity. The binding region seems located on the C-terminal portion of the Aα and Bβ chains because (1) its function is gradually destroyed by progressive degradation with plasmin and (2) neither purified fragment E nor the N-terminal disulfide knot binds to staphylococci. These findings were supported by experiments with abnormal variants of fibrinogen. Fibrinogen Detroit, with a defect in the N-terminal part of the Aα chain, retained full clumping reactivity toward the staphylococcal receptor, as did fibrinogen Paris I, which manifests a defect in the C-terminal portion of the γ chain. After reduction and carboxymethylation, fibrinogen retained its ability to bind to staphylococci; however, the clumping reactivity was lost, suggesting that disulfide bonds contribute not to the binding properties of fibrinogen but only to its ability to clump. The clumping reaction occurred in the presence of diisopropylfluorophosphate at a concentration that inactivated staphylocoagulase and thrombin, indicating that the clumping reaction does not depend on the enzymatic activity of a serine protease type. Other factors, such as pH, chelators, polyanions, and detergents, were examined for their influence on the clumping reaction. The existence of a binding region(s) for staphylococci provides a basis for their use in measurement of normal and abnormal variants of human fibrinogen and its derivatives. |
