Blood, Vol. 95 No. 3 (February 1), 2000:
pp. 1086-1092
Polytrauma induces increased expression of pyruvate kinase in
neutrophils
Rudolf Oehler,
Gertrude Weingartmann,
Nicole Manhart,
Ulrich Salzer,
Michael Meissner,
Werner Schlegel,
Andreas Spittler,
Michael Bergmann,
Daniela Kandioler,
Christiane Oismüller,
Heidi M. Struse, and
Erich Roth
From the Surgical Research Laboratories, Institute of Biochemistry,
Institute of Tumor Biology-Cancer Research, and Department of
Anesthesiology, University of Vienna, Vienna, Austria, and the
Department of Human Biological Chemistry and Genetics, University of
Texas, Galveston.
Polytrauma (PT) leads to systemic activation of polymorphonuclear
neutrophils (PMNs). Organ damage commonly found in these patients is
ascribed to respiratory bursts of activated PMNs. With the use of
sodium dodecyl sulfate-polyacrylamide gel electrophoresis, PMN
extracts from PT patients were found to contain a clear protein band
not seen in control PMNs from healthy volunteers. This band was
identified by amino acid sequencing and Western blotting as pyruvate
kinase (PK). Enzymatic assays revealed a 600-fold increase in PK
activity in PMNs of PT patients, with the highest levels occurring
between the fifth and seventh posttraumatic day. In lymphocytes, no
such increase was detectable. As PK is a major regulatory enzyme in
glycolysis, glucose-dependent lactate production in PMNs from PT
patients was assayed. These cells showed a higher glycolytic lactate
production than controls. It was additionally demonstrated that acute
activation of respiratory burst activity depends mainly on breakdown of
glucose to lactate via the pentose-phosphate pathway and glycolysis. In
PMNs from PT patients, this glucose-dependent respiratory burst
activity was more than twofold higher than in controls. The increase in
expression and activity of PK in PMNs from PT patients may contribute
to the high glucose-dependent respiratory burst activity seen in these cells.
