Mechanisms of tumor cell capture by activated macrophages: evidence for involvement of lymphocyte function-associated (LFA)-1 antigen.
The lymphocyte function-associated (LFA)-1 molecule is expressed on certain populations of macrophages that have an augmented capacity to capture tumor cells. Accordingly, we analyzed the role of LFA-1 in the establishment of such cell-cell interactions. F(ab')2 fragments of the M17/4, anti-LFA-1 monoclonal antibody (MAb) inhibited the interaction between activated macrophages and tumor cells by up to 80% in a dose-dependent manner. The anti-LFA-1 MAb reduced (between 55 to 79%) the number of P815, LSTRA, or EL-4 tumor cells bound to trypsin-sensitive structures on bacillus Calmette Guerin activated macrophages. The inhibition appeared selective, because a F(ab')2 fragment of anti-Mac-1 did not inhibit such binding. Inhibition of tumor cell capture could be observed as soon as 15 min after the onset of the cell-cell interaction between activated macrophages and tumor cells. Optimal inhibition occurred when both tumor targets and macrophages were precoated with the MAb. Although P815, LSTRA, EL-4, and BW5147 tumor cells all expressed LFA-1, only the first three but not BW5147 cells were bound by activated macrophages. Furthermore, endotoxin-pulsed macrophages elicited by thioglycollate broth expressed the LFA-1 antigen but did not exhibit selective tumor cell capture. Finally, anti-LFA-1 inhibited the development of weak into strong binding. Taken together, the results suggest that LFA-1 molecules can participate in the interaction between activated macrophages and neoplastic cells.
G
G
Strassmann
T A
TA
Springer
S D
SD
Somers
D O
DO
Adams
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D000954:Antigens, Surface / Q000276:immunology*; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D002450:Cell Communication; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes; D005260:Female; D007111:Immunity, Cellular; D007140:Immunoglobulin Fab Fragments / Q000502:physiology; D016169:Lymphocyte Function-Associated Antigen-1; D008223:Lymphoma / Q000276:immunology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology; D012515:Mast-Cell Sarcoma / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013945:Thymoma / Q000276:immunology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D016169:Lymphocyte Function-Associated Antigen-1