Enhancement of lung tumor colony formation by treatment of mice with monoclonal antibodies to pulmonary capillary endothelial cells.
Two rat monoclonal antibodies, 34A and 201B, have been isolated and shown to bind preferentially to capillary endothelial cells in the lung. Administration of these antibodies to mice increases the number of lung colonies derived from i.v. injection of tumor cells. The antibodies increase lung colonization in C57BL/6 mice following i.v. injection of B16-F10 melanoma cells and in BALB/c mice following injection of line 1 lung carcinoma cells. Neither 34A nor 201B monoclonal antibody binds to B16 melanoma or line 1 carcinoma and so must exert its effect by interaction with endothelial cells. Antibodies injected i.v., s.c., or i.p. are active from 1 h to 1 wk if injected before cell injection. The effect is optimal when 0.1 ml of ascites fluid containing 120 micrograms of antigen binding capacity of both MoAbs 34A and 201B is injected. Significant damage to endothelial cells could not be documented by histopathological examination at the light microscope level or by protein leakage into the air space as measured by lung lavage. However, electron micrographs taken 3 h after monoclonal antibody injection show minor damage to endothelial cell membranes throughout the lung with some areas of mild edema. The increased colonization may be mediated by this subtle damage to endothelial cells, or antibody interactions with endothelial cells may trigger secondary reactions such as altered expression of growth factors.
Kennel
S J
SJ
Biology Division, Oak Ridge National Laboratory, Tennessee 37831.
Lankford
T K
TK
Ullrich
R L
RL
Jamasbi
R J
RJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002196:Capillaries / Q000276:immunology; D002450:Cell Communication; D004730:Endothelium, Vascular / Q000276:immunology* / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D008168:Lung / Q000098:blood supply* / Q000473:pathology / Q000648:ultrastructure; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
D000911:Antibodies, Monoclonal