INHIBITORS OF PLASMINOGEN-ACTIVATOR IN NEUTROPHILS AND MONONUCLEAR-CELLS FROM SEPTIC PATIENTS

Leucocytes, both polymorphs and mononuclear cells, play a variety of r oles in the evolution of human response to sepsis, both local and gene ralised. In this study, inhibitors of plasminogen activator were measu red in leucocytes from normal and septic patients. Plasminogen activat or inhibitor-1 (PAI-1) was identified in polymorphs from normal indivi duals and levels rose significantly in polymorphs from septic patients : neutrophils from normal subjects did not contain PAI-2 but this prot ein was detectable in significant quantities in polymorph preparations from septic patients. In contrast, mononuclear cells from normal and septic patients contained no detectable quantities of PAI-1. Significa nt amounts of PAI-2 were present in normal mononuclear cells, and the levels rose significantly in monocytes from septic patients. PAI-2 is thus here identified in human subjects, distinct from those with pregn ancy or malignancy, as playing a role in a pathological process. The i ncreased levels of both inhibitors produced by leucocytes may clearly contribute directly to the persistence of fibrin, a characteristic fea ture of the response to infection, local or general; they may thus par ticipate in successful localisation of infections (abscess formation e tc.) and in the evolution of the major systemic complications of disse minated sepsis characterised by microvascular occlusion by fibrin such as rend failure, shock lung or digital ischaemia.