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Blood, Vol. 96 No. 3 (August 1), 2000:
pp. 834-839
Induction of monocyte- and T-cell-attracting chemokines in the
lung during the generation of idiopathic pneumonia syndrome
following allogeneic murine bone marrow transplantation
Angela Panoskaltsis-Mortari,
Robert M. Strieter,
John R. Hermanson,
Konstantin V. Fegeding,
William J. Murphy,
Catherine L. Farrell,
David L. Lacey, and
Bruce R. Blazar
From the University of Minnesota Cancer Center and Department of
Pediatrics, Division of Hematology, Oncology, Blood and Marrow
Transplant Program, University of Minnesota, Minneapolis, MN;
Department of Medicine, Division of Pulmonary and Critical Care
Medicine, UCLA School of Medicine, Los Angeles, CA; Department of
Pathology, Walter Reed Army Institute, Washington, DC;
SAIC Frederick, NCI-FCRDC, Frederick, MD; and
Amgen Inc, Thousand Oaks, CA.
Idiopathic pneumonia syndrome (IPS) is a significant complication
following bone marrow transplantation (BMT). We have developed a murine
model in which severe IPS is induced by pre-BMT conditioning and
allogeneic T cells and is characterized by the recruitment of host
monocytes and donor T cells into the lung by day 7 post-BMT. Chemokines
regulate cellular recruitment and the migration of cells into
inflammatory lesions. In this study, we examined the profiles of
chemokines produced locally in the lung (parenchyma and bronchoalveolar
lavage fluid) and systemically (serum) during the generation of IPS in
the peri-BMT period. Protein and messenger RNA (mRNA) levels of CC
chemokines (monocyte/lymphocyte attractants), especially monocyte
chemoattractant protein (MCP)-1, macrophage inflammatory protein
(MIP)-1 , RANTES (regulated upon activation normal T-cell expressed
and secreted), and C10, were preferentially induced in the lung by day
7 postallogeneic BMT. In addition, there was an increase in mRNA for
IP-10 (a monocyte and Th1-cell chemoattractant). The CXC chemokines
MIP-2 and KC, known neutrophil attractants, were moderately elevated.
For the most part, these increases in chemokines were dependent on the
coinfusion of allogeneic T cells with the BM inoculum. Ribonuclease
protection assay and in situ hybridization analyses post-BMT showed
that the lung was a major producer of MCP-1, a potent inducer of
monocyte chemotaxis. Increases in MCP-1 levels in the lung preceded
host APC influx whereas MIP-1 levels accompanied donor T-cell
infiltration. In summary, we have shown that monocyte- and
T-cell-attracting chemokines are associated with monocyte and
T-cell recruitment during IPS.
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