Hemophagocytic macrophages constitute a major compartment of heme oxygenase expression in sepsis.
OBJECTIVE
Uncontrolled macrophage activation with hemophagocytosis is a distinctive feature of hemophagocytic syndromes (HPS). We examined whether lympho-histiocytic infiltration of the bone marrow and liver, as well as hemo-/erythrophagocytosis also occurs during sepsis and whether this process could account for the increased production of anti-inflammatory heme-oxygenase (HO-1) products observed during sepsis.


METHODS
Hemophagocytosis and expression of CD163, HO-1, ferritin as well as CD8 and granzyme-B were examined in post-mortem bone marrow samples from 28 patients with sepsis and from eight control patients.


RESULTS
Comparison of samples from non-septic patients with samples from patients with fatal sepsis revealed that the latter group displayed dense lympho-histiocytic bone marrow infiltration with CD163(+)/HO-1(+)/ferritin(+) macrophages as well as with CD8(+) and granzyme-B(+) T-cells. Hemophagocytosis with prominent phagocytosis of erythroid cells was readily apparent in septic patients, implying that this process is a likely stimulus for the up-regulation of macrophage HO-1 expression.


CONCLUSIONS
Lympho-histiocytic activation with hemophagocytosis is a shared pathophysiologic mechanism in HPS and sepsis. Furthermore, the association of hemophagocytosis with an increase in HO-1 expression may indicate a novel role for this apparently futile process as a negative regulator of inflammation.
Schaer
Dominik J
DJ
Department of Medicine, University Hospital, Zurich, Switzerland. dominik.schaer@usz.ch.
Schaer
Christian A
CA
Schoedon
Gabriele
G
Imhof
Alexander
A
Kurrer
Michael O
MO
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D001853:Bone Marrow / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D041905:Erythroid Cells / Q000201:enzymology / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008264:Macrophages / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010587:Phagocytosis / Q000235:genetics; D018805:Sepsis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics
D015415:Biomarkers; D051547:Heme Oxygenase-1