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MIP-1[alpha]
Expression in Tissues from Patients with Hemophagocytic Syndrome |
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Julie Teruya-Feldstein,
Joyce Setsuda, Xu Yao, Douglas W. Kingma, Stephen Straus, Giovanna Tosato,
and Elaine S. Jaffe |
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Laboratory
of Pathology, Hematopathology Section, National Cancer Institute, National
Institutes of Health (JTF, JS, XY, DWK, ESJ); Laboratory of Clinical Investigation,
National Institute of Allergy and Infectious Diseases (SS); and the Center
for Biologics Evaluation and Research, Food and Drug Administration, Bethesda,
Maryland (GT) |
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SUMMARY: Hemophagocytic
syndrome (HPS) is a clinicopathologic syndrome that can be precipitated
by a variety of causes and is characterized by a systemic activation of
macrophages, which are induced to undergo phagocytosis. Chemokines play
an important role in the inflammatory cell recruitment into tissues. We
examined the expression of chemokines and cytokines in tissues exhibiting
histologic evidence of HPS in a variety of settings: peripheral T-cell lymphoma,
three patients; nasal T/NK cell lymphoma, one patient; subcutaneous panniculitis-like
T-cell lymphoma, one patient; and chronic EBV infection, one patient. Compared
with control tissues, we found elevated macrophage inflammatory protein-1[alpha]
(MIP-1[alpha]) and interferon-[gamma] (IFN-[gamma]) expression, but not
macrophage-derived chemotactic factor (MDC) or TNF-[alpha], in tissues of
patients with HPS irrespective of the cause or setting. MIP-1[alpha] can
promote macrophage chemotaxis and IFN-[gamma] promotes macrophage activation.
Elevated expression of IP-10 and monokine induced by IFN-[gamma] (Mig) was
also detected in tissues exhibiting features of HPS, providing an explanation
for the occurrence of chemoattraction of T-cells and NK cells. Immunohistochemical
analysis of tissues with evidence of phagocytic activity in that site showed
MIP-1[alpha] characteristically localized to endothelial cells of blood
vessels and splenic sinuses, lymphocytes, and macrophages. These results
provide evidence for MIP-1[alpha] chemokine expression in tissues from patients
with HPS and suggest that MIP-1[alpha] may play an important role in the
pathogenesis of the hemophagocytic syndrome. |
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