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Prepublished online as a Blood First Edition Paper on August 8, 2002; DOI 10.1182/blood-2002-05-1552.
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Blood, 15 December 2002, Vol. 100, No. 13, pp. 4660-4667
TRANSPLANTATION
Myeloid progenitors protect against invasive aspergillosis and
Pseudomonas aeruginosa infection following hematopoietic
stem cell transplantation
Andrew BitMansour,
Stacy M. Burns,
David Traver,
Koichi Akashi,
Christopher H. Contag,
Irving L. Weissman, and
Janice M. Y. Brown
From the Divisions of Bone Marrow Transplantation and
Infectious Diseases, Department of Medicine; Department of Pathology;
and Departments of Pediatrics and Microbiology and Immunology; Stanford
University School of Medicine, CA.
Myelotoxic treatments for oncologic diseases are often complicated
by neutropenia, which renders patients susceptible to potentially lethal infections. In these studies of murine hematopoietic stem cell
transplantation (HSCT), cotransplantation of lineage-restricted progenitors known as common myeloid progenitors (CMP) and
granulocyte-monocyte progenitors (GMP) protects against death following
otherwise lethal challenge with either of 2 pathogens associated with
neutropenia: Aspergillus fumigatus and Pseudomonas
aeruginosa. Cotransplantation of CMP/GMP resulted in a
significant and rapid increase in the absolute number of myeloid cells
in the spleen, most of which were derived from the donor CMP/GMP.
Despite persistent peripheral neutropenia, improved survival correlated
with the measurable appearance of progenitor-derived myeloid cells in
the spleen. A marked reduction or elimination of tissue pathogen load
was confirmed by culture and correlated with survival. Localization of
infection by P aeruginosa and extent of disease was
also assessed by in vivo bioluminescent imaging using a strain of
P aeruginosa engineered to constitutively express a
bacterial luciferase. Imaging confirmed that transplantation with a
graft containing hematopoietic stem cells and CMP/GMP reduced the
bacterial load as early as 18 hours after infection. These results
demonstrate that enhanced reconstitution of a tissue myeloid pool
offers protection against lethal challenge with serious fungal and
bacterial pathogens.

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