INTER-ALPHA-INHIBITOR AS MARKER FOR NEUTROPHIL PROTEINASE ACTIVITY - AN IN-VITRO INVESTIGATION

Human neutrophil proteinases have been implicated in the pathogenesis of a wide variety of inflammatory diseases. The degradation of plasma proteins such as coagulation and fibrinolysis factors has been attribu ted to the excessive release of elastase in septicemia and in other co nditions in which heightened proteolysis occurs. Inter-alpha-inhibitor (l alpha l) is particularly sensitive to cleavage by leukocyte protei nases. For this reason, the determination of I alpha I has been propos ed as a method for evaluating plasma protein proteolysis by neutrophil enzymes. In this article we provide evidence that intact residual I a lpha I can be accurately quantified by enzyme-linked immunosorbent ass ay (ELISA) determination without interference from fragments released from I alpha I by incubation with triggered neutrophils. We demonstrat e that under these conditions I alpha I was quickly and steadily prote olyzed in a cell dose-dependent manner. alpha-1 proteinase inhibitor ( alpha 1PI) partially protected I alpha I; however, the proteolysis per sisted when I alpha I was incubated with stimulated neutrophils in the presence of a large relative excess of alpha 1PI over the amount of e lastase theoretically present in cells. For the same amount of alpha 1 PI, serum provided a better protection than alpha 1PI atone but did no t completely inhibit the I alpha I degradation, Therefore, ELISA deter mination of I alpha I might be useful for monitoring the in vivo activ ity of neutrophil proteinases in systemic proteolytic states.