INHIBITION OF NEUTROPHIL SUPEROXIDE PRODUCTION BY HUMAN PLASMA ALPHA-1-ANTITRYPSIN

We report here that human plasma alpha-1-antitrypsin (alpha-1-AT) inhi bited human neutrophil O2.- release elicited by a variety of stimulant s. In comparison, the inhibitory capacities of two serine protease inh ibitors, L-1-tosylamide 2-phenylethyl chloromethyl ketone (TPCK) and s oybean trypsin inhibitor (SBTI), and the human recombinant alpha-1-AT mutant, alpha-1-AT-Arg358 were in the order: alpha-1-AT almost-equal-t o TPCK much greater than alpha-1-AT-Arg358 > SBTI when cells were stim ulated with concanavalin A plus cytochalasin E. These data suggest tha t, in human inflammatory fluids containing relatively high concentrati ons of alpha-1-AT (such as rheumatoid arthritis synovial fluid), (i) a lpha-1-AT may down-regulate the inflammatory process by inhibiting the neutrophil respiratory burst and (ii) serpin oxidation by neutrophil- released reactive oxygen species is unlikely to occur.