Determination of Leukocyte Elastase Concentration in Plasma and Serum by a Simple Method Using a Specific Synthetic Substrate

Abstract

The concentration of leukocyte elastase (ELP) in plasma and serum was determined by an amidolysis method using a specific synthetic substrate for ELP, Suc-Ala-Tyr-Leu-Val-pNA. Results were compared with those using ELISA. ELP levels in plasma from healthy donors were similar to those determined by ELISA; however, the levels in serum were lower than those determined by ELISA. Correlation coefficients of ELP levels in plasma and serum as measured by the two methods were 0.75 (amidolysis) and 0.90 (ELISA). On the other hand, the correlation coefficient between serum ELP by the two methods was 0.83. Half of the ELP levels in plasma from 150 patients and serum from 400 patients were significantly elevated when compared with those from healthy donors, and the ELP elevation determined by amidolytic assay correlated with some variables in blood, namely fibrin(ogen)-degraded products, fibrinogen, GOT, GPT, γ-GTP, LDH and leucine aminopeptidase. Despite the fact that the amidolysis method detects the α₂-macroglobulin-ELP complex while ELISA detects the α₁-antitrypsin-ELP complex, a comparative study showed amidolysis to provide sufficiently sensitive measurement of both plasma and serum ELP.

Elastase II Gene Encoding as Inflammatory Molecules in Acute Myeloblastic Leukemia

“…No mutations were identified in at least 30 healthy controls, but 50% frequency in polymorphisms was detected in healthy individuals. These results are compatible with those published previously, showing that a high level of ELA2 is caused in AML (14)(15)(22)(23)(24). The pathogenicity of mutations in ELA2 remains a mystery.…”

Motility, proliferation, and egress to the circulation of human AML cells are elastase dependent in NOD/SCID chimeric mice

“…Recently, others and we began to identify the factors and mechanisms that control the emigration of normal cells from the BM into the circulation. The finding that elastase, among other proteolytic enzymes such as cathepsin G and MMPs, participates in the process of G-CSF-induced mobilization of normal stem cells, progenitors, and maturing cells 29,30 led us to hypothesize that the abnormally high levels of elastase in AML patients' plasma 17,19 may facilitate the cells' egress into the circulation.…”

“…15,16 Previous studies reported high levels of intracellular elastase activity and secretion of elastase protein by AML cells. [17][18][19] Evidence recently emerged that elastase has a major role in the development of myeloid leukemias. Elastase produced by chronic myelogenous leukemia (CML) neutrophils preferentially suppresses normal hematopoiesis.…”

Neutrophil elastase enzymatically antagonizes the in vitro action of G-CSF: implications for the regulation of granulopoiesis

“…Normally serum neutrophil elastase levels are in the order of 200 ng/mL, but much of it is complexed with serpins and therefore is inactive. However, elastase levels correlate directly with the number of peripheral blood neutrophils, 18 and 10 6 neutrophils can release up to 2 g/mL elastase. 19 Furthermore, changes in elastase accompany the administration of G-CSF.…”

“…18,29,30 The question arises whether an inhibitory effect of elastase on normal granulopoiesis contributes to the dominance of a G-CSF-independent leukemic clone or, alternatively, whether elastase release by leukemic cells could contribute to the maturation arrest of a G-CSF-sensitive leukemic blast cell.…”