In situ activation of mouse lung macrophages by coadministration of liposomes containing the lipopeptide CGP 31362 and interleukin 2 involves interaction with T lymphocytes and natural killer cells.
These studies were undertaken to determine the mechanism for augmented tumoricidal activity of alveolar macrophages (AM) in mice injected intravenously with multilamellar liposomes containing a lipopeptide analogue of Gram-negative bacteria cell wall (MLV-CGP 31362) and intraperitoneally with interleukin 2 (IL-2). BALB/c mice were injected into the kidney with syngeneic renal carcinoma cells. Ten days later, this kidney was resected, and the mice were treated intravenously with MLV-CGP 31362 and/or intraperitoneally with IL-2. Treatment with MLV-CGP 31362 led to a reduction in the number of lung metastases, whereas treatment with IL-2 alone did not. The coadministration of intravenous liposomes and intraperitoneal IL-2 produced significant eradication of lung metastases. MLV-CGP 31362 (iv) and IL-2 (ip) were injected both into control immune-competent and nude mice or into mice whose natural killer (NK) cells had been depleted by systemic administration of anti-asialo GM1 antibodies. MLV-CGP 31362 activated tumoricidal properties in AM of all groups of mice. The additive tumoricidal activation of AM by IL-2 was associated with its effects on both T cells and NK cells.
Utsugi
T
T
Department of Cell Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Dinney
C P
CP
Killion
J J
JJ
Brown
D
D
Fidler
I J
IJ
D000818:Animals; D002450:Cell Communication / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004337:Drug Carriers; D007376:Interleukin-2 / Q000008:administration & dosage*; D007694:Killer Cells, Natural / Q000187:drug effects*; D008081:Liposomes; D008262:Macrophage Activation / Q000187:drug effects*; D016676:Macrophages, Alveolar / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009842:Oligopeptides / Q000008:administration & dosage*; D010446:Peptide Fragments / Q000008:administration & dosage*; D013601:T-Lymphocytes / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D004337:Drug Carriers; D007376:Interleukin-2; D008081:Liposomes; D009842:Oligopeptides; D010446:Peptide Fragments; C068423:CGP 31362