Serine proteases are ubiquitous and are fundamentally responsible for many of the control processes in plasma. Hemostasis and
inflammation have the same evolutionary origins and developed as host-defense mechanisms. This article highlights this development and defines the role of
serine proteases in the complex
inflammation and coagulation cascades that have evolved to maintain homeostasis. Generation of the
serine protease thrombin plays a pivotal role in the regulation of many functions and is able to initiate activation and release of a number of humoral mediators involved in the inflammatory and
hemostatic systems. Control processes are required to limit coagulation and
inflammation to sites of injury, and a number of these have at their center inhibitors of
serine proteases (
SERPIN). A vast number of inhibitors are found throughout nature. In addition to these naturally occurring
SERPINs, a number of others are available for administration to both animals and humans. Of these,
aprotinin is a complex
polypeptide; there are other chlormethyl
ketones and small synthetic agents that also act as potent
SERPINs. A second group of compounds are not
protein inhibitors but have a broad spectrum of inhibition, e.g., a
gabexate mesylate (
FOY) and nefamostat (FUTHAN). The profound actions of
aprotinin, FUTHAN, and
FOY to inhibit
bleeding and prevent the need for donor blood are well known. The potential role of these agents, particularly
aprotinin, to reduce the inflammatory effects of cardiac and other kinds of surgery is considered. The data on
SERPINs actions to reduce neutrophil-induced tissue injury are reviewed, with particular reference to the inflammatory events that occur during surgery with
cardiopulmonary bypass.