LAUSR

There are already many links between hemostasis and innate immunity, which have a strong connection in terms of a common evolutionary ancestry as immediate responses to injury. In addition to the commonalities between coagulation and inflammation, fibrin clots play an important role in host antimicrobial defense. Strong evidence comes from research using mice lacking fibrinogen or with a mutant form of fibrinogen that cannot form fibrin, with the consequence of impaired bacterial clearance and decreased survival after infection with certain bacteria [1]. Fibrin networks act as a physical barrier to bacterial invasion. Also, some immune and inflammatory cells, such as neutrophils, are activated by binding to fibrin(ogen). Conversely, some bacteria have evolved the ability to bind specifically to fibrin to evade the immune system by forming resistant bacterial biofilms. The recent report of fibrin biofilms at the liquid–air interface of fibrin clots provides another mechanism for antimicrobial protection [2]. Although the discovery of these fibrin biofilms may appear unexpected, their existence on the surface of in vitro clots has been known for quite some time. Since we worked out methods for preparing samples and started doing scanning electron microcopy of clots, we have seen these fibrin films for nearly 35 years. However, during all that time, we regarded these films as an artifact of surface drying because this phenomenon could be ameliorated by formation of clots in a humid chamber. During this time, as we taught many other scientists how to prepare clots for scanning electron microscopy, they all also observed such films. Thus, the real breakthrough here is not the observation, but the insight that these films could have some biological significance. Indeed, because such films are difficult to prevent in vitro, in retrospect it seems likely that they would occur in vivo at liquid–air interfaces, but this possibility had never been considered and studied previously. On a very superficial level, these fibrin films might be suspected to have some structural similarities to the ultrathin fibrin sheets formed over channels that were described about 10 years ago [3]. However, these fibrin sheets occur under quite different circumstances. They polymerize on hydrophobic or hydrophilic surfaces, usually at very low fibrinogen and thrombin concentrations. They are molecularly thin and extensive, but can fold and roll up into fibers. The main mechanistic similarity is that both the fibrin biofilms and the ultra-thin fibrin sheets are formed as a result of physical association of fibrin(ogen) molecules distinct from the classical half-staggered polymerization.