Induction of monocyte- and T-cell-attracting chemokines in the lung duringthe generation of idiopathic pneumonia syndrome following allogeneic murine bone marrow transplantation

Idiopathic pneumonia syndrome (IPS) is a significant complication following bone marrow transplantation (BMT), We have developed a murine model in whi ch severe IFS is induced by pre-BMT conditioning and allogeneic T cells and is characterized by the recruitment of host monocytes and donor T cells in to the lung by day 7 post-BMT. Chemokines regulate cellular recruitment and the migration of cells into inflammatory lesions. In this study, we examin ed the profiles of chemokines produced locally in the lung (parenchyma and bronchoalveolar lavage fluid) and systemically (serum) during the generatio n of IFS in the peri-BMT period. Protein and messenger RNA (mRNA) levels of CC chemokines (monocyte/lymphocyte attractants), especially monocyte chemo attractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1 alpha, RANTES (regulated upon activation normal T-cell expressed and secreted), an d 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-c ell chemoattractant). The CXC chemokines MIP-2 and KC, known neutrophil att ractants, were moderately elevated. Far the most part, these increases in c hemokines were dependent on the coinfusion of allogeneic T cells with the B M inoculum, Ribonuclease protection assay end in situ hybridization analyse s post-BMT showed that the lung was a major producer of MCP-1, a potent ind ucer of monocyte chemotaxis, Increases in MCP-1 levels in the lung preceded host APC influx whereas MIP-1 alpha levels accompanied donor T-cell infilt ration. In summary, we have shown that monocyte- and T-cell-attracting chem okines are associated with monocyte and T-cell recruitment during IFS. (C) 2000 by The American Society of Hematology.