ALLOGENEIC BLOOD-TRANSFUSION REDUCES MURINE PULMONARY NATURAL-KILLER (NK) ACTIVITY AND ENHANCES LUNG METASTASIS OF A SYNGENEIC TUMOR

A model was established whereby C57BL/6 (B6) blood injected i.v. into C3H mice 7 days prior to i.v. injection Of syngeneic UV-2237 tumour ce lls significantly increased the number of pulmonary metastases counted 21 days later as compared with levels observed in mice treated with s aline, C3H or NZW blood or SRBC. This regimen of B6 allogeneic blood t ransfusion of C3H mice also significantly depressed splenic and pulmon ary NK activity as assayed by lysis of Cr-51 YAC-1 in vitro and by cle arance of In-111 YAC-1 in vivo respectively. Anti-asialo GM1 treatment , which depletes NK activity in vivo, and Poly I:C treatment, which en hances NK activity in vivo, were associated with significantly increas ed and decreased pulmonary metastasis of UV-2237, respectively, in C3H mice. Depletion of CD4+ and CD8+ T cells had no effect. Cyclophospham ide pre-treatment which, among other effects, depletes NK cells, signi ficantly increased pulmonary metastasis of UV-2237 in C3H mice. This w as corrected by adoptive transfer of normal C3H spleen cells but not s pleen cells from anti-asialo GM1-treated C3H mice or B6-blood-transfus ed C3H mice. Furthermore, a 1:1 mixture of normal C3H spleen cells wit h spleen cells from B6-blood-transfused C3H mice also failed to recons titute the cyclophosphamide-pre-treated C3H mice. We conclude that all ogeneic blood transfusion augments pulmonary metastasis of the UV-2237 sarcoma in C3H mice and that the mechanism involves suppression of NK activity. (C) 1993 Wiley-Liss, Inc.