Am. J. Respir. Cell Mol. Biol., Vol 11, No. 1, Jul 1994, 35-41.
Thrombin inhibition by fetal distal lung epithelium is different in fetal and adult plasma
M Andrew, L Berry and H O'Brodovich
Department of Pediatrics, University of Toronto, Hospital for Sick Children's Research Institute, Ontario, Canada.
Intra-alveolar fibrin deposition is a cardinal feature of neonatal
respiratory distress syndrome and likely contributes to short-term and
long-term morbidity. Previous studies have shown that fetal distal lung
epithelial cell (FDLE) surfaces express procoagulant activity when
incubated with adult plasma and may therefore provide one mechanism by
which fibrin is generated. However, plasma concentrations of prothrombin
and thrombin inhibitors differ significantly at birth and during the first
weeks of life compared with adult values. Therefore, we measured
thrombin-generating capacity and inhibitor complex formation in cord and
adult plasma incubated in the presence of FDLE. Although starting cord
plasma concentrations of prothrombin were 43% of adult values, the amount
of thrombin generated was decreased by only 21%. When cord plasma
concentrations of prothrombin were selectively increased to adult values,
the amount of thrombin generated surpassed adult plasma by 89%. The latter
observations suggested that thrombin inhibition was impaired in cord plasma
compared with adult plasma and supplementation of cord plasma with
antithrombin III (ATIII) as well as prothrombin returned thrombin
generation to adult levels. However, the percentage of thrombin complexed
to inhibitors (59%) at the completion of the experiments was similar in
cord, cord plus prothrombin, cord plus prothrombin plus ATIII, and adult
plasmas. Although a higher proportion of thrombin was inhibited by alpha
2-macroglobulin (alpha 2M) in cord plasma and cord plasma plus prothrombin,
this did not compensate for the decreased amount of thrombin inhibited by
ATIII. When cord plasma was supplemented with ATIII as well as prothrombin,
the proportions of thrombin complexed by the different inhibitors were
similar to those of adult plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
