Proliferation of pulmonary macrophages during the early phase of an acute graft-versus-host reaction in mice.

Abstract

The pulmonary response was investigated during the early lymphoproliferative phase of an acute graft-versus-host (GVH) reaction induced in (C57BL/6 x A/J)F1 hybrid mice by iv injection of 50 x 10(6) A/J spleen and lymph node cells. The GVH reaction was monitored by measuring splenomegaly and immunosuppression. Animals were sacrificed after 5, 7, 11, and 16 d and bronchoalveolar lavage was performed; on each day a significant increase in the number of alveolar macrophages (AM) was seen, whereas no increase was found in other inflammatory cells. In lung sections, interstitial mononuclear cell infiltrates were seen around airways and pulmonary veins on d 11 and in alveolar septae on d 16. The kinetics of cell proliferation was evaluated in lung, liver, and peritoneum of mice with GVHR reactions by injecting [3H] thymidine 1 h before sacrifice. Autoradiographs revealed a marked increase in the number of labeled AM, pulmonary interstitial cells, Kuppfer cells, peritoneal macrophages, and intravascular monocytes. The results indicate that the GVH reaction causes a proliferative response of pulmonary macrophages early in its course. This stimulus appears to by systemic, since resident macrophages in other organs show a similar response. It is possible that local macrophage proliferation and the subsequent activation of these cells may play a role in the cellular mechanism of tissue injury seen during later stages of the reaction.