Polymorphonuclear leukocyte dysregulation during the systemic inflammatory
response syndrome
HH Simms and R D'Amico
Department of Surgery, Brown University School of Medicine, Rhode Island
Hospital, Providence 02903.
Altered polymorphonuclear leukocyte (PMN) function is thought to contribute
to organ dysfunction during the systemic inflammatory response syndrome
(SIRS). To test this hypothesis, we evaluated whole blood PMN function
adherent to fibronectin or laminin in patients with mild or severe acute
pancreatitis as a paradigm for sirs. Whole-blood PMN intracellular H2O2
production, expression of CD32w (Fc gamma R II), CD16 (Fc gamma R III), and
phagocytosis were performed using dichlorofluorescein diacetate,
fluorescein isothiocyanate-labeled anti- CD32w, CD16, and serum-opsonized
fluorescent microspheres. Group I (n x 7) represents normal control
individuals; group II (n x 11) represents patients with mild acute
pancreatitis. Group III (n x 15) represents critically ill patients with
severe acute pancreatitis. Adherence of PMN from groups I and II to matrix
proteins resulted in a 5% to 20% increase in each PMN function assayed
whereas adherence of PMN from group III to matrix proteins resulted in 50%
to 75% increases in each PMN function assayed. Pertussis toxin,
pentoxifylline, and dibutyryl cyclic adenosine monophosphate (cAMP) each
reduced group I-II H2O2 production and phagocytosis. Pentoxifylline and
dibutyryl cAMP but not pertussis toxin reduced group III H2O2 production.
Both intracellular H2O2 and phagocytosis assays from group III but not
groups I-II showed exaggerated upregulation when exposed to NaF (4 mmol/L).
Anti- interleukin-6 reduced the increase in intracellular H2O2 production
in group III patients and significantly altered the exaggerated oxidative
response to NaF. Longitudinal studies of group III whole-blood PMN showed
persistent upregulation of intracellular H2O2 production in those patients
whose hospital courses were complicated by multiple system organ failure.
These results demonstrate abnormal whole blood PMN function during the
systemic inflammatory response syndrome in the presence of fibronectin, or
laminin and that this is mediated in part via a pertussis toxin insensitive
altered guanosine triphosphate- binding protein.
Volume 83,
Issue 5,
pp. 1398-1407,
03/01/1994
Copyright © 1994 by The American Society of Hematology
