Molecular weight alterations of alpha-1 proteinase inhibitor in equine bronchoalveolar lavage fluid.

The equine alpha-1 proteinase inhibitor (alpha 1PI) system differs from that of man in that the equine system consists of four closely-linked genes (Spi1-Spi4) whereas in man, a single gene encodes for alpha 1PI. We have previously found differences in the proportion of the Spi proteins in equine serum and bronchoalveolar lavage fluid (BALF). We therefore wished to determine whether, as reported in man, there was any molecular weight difference between the Spi proteins in serum and BALF. alpha 1PI and albumin from equine BALF migrated further towards the anode compared with serum alpha 1PI on native polyacrylamide gel electrophoresis (PAGE) although the difference was only significant for alpha 1PI. Sodium dodecyl sulphate-PAGE (SDS-PAGE) showed that a mean decrease in molecular weight of 1.5 kDa for alpha 1PI and 1.3 kDa for albumin had occurred in BALF. These findings were observed in control animals and in those with symptomatic or asymptomatic chronic obstructive pulmonary disease. The mechanism of this decrease in molecular weight of alpha 1PI is likely to differ from reports of alpha 1PI cleavage by bacterial proteinases in man since the molecular weight change was relatively small and loss of trypsin inhibitory activity did not occur. Nor, in our system, was there evidence of bacterial infection. Damage by endogenous proteinases or glycosidases at a site other than the reactive site may be involved but the resultant effect on the efficiency of the antiproteinase screen of the lower respiratory tract is uncertain.