Quantitative analysis of the effect of cell type and cellular differentiation on protective antigen binding to human target cells.
We quantitatively measured protective antigen (PA) binding to human cells targeted by anthrax lethal toxin (LT). Affinities were less than 50 nM for all cells, but differentiated cells (macrophages and neutrophils) had significantly increased PA binding and endothelial cells demonstrated the most binding. Combined with the function of such cells, this suggests that PA receptors interact with the extracellular matrix and that differentiation increases the number of PA-specific receptors, which supports previously observed differentiation-induced LT susceptibility. Our results quantifiably confirm that the generality of PA binding will complicate its use as a tumor targeting agent.
Deshpande
Alina
A
Decisions Applications Division, Los Alamos National Laboratory, MS M888, Los Alamos, NM 87545, USA.
Hammon
Rebecca J
RJ
Sanders
Claire K
CK
Graves
Steven W
SW
D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology; D001427:Bacterial Toxins / Q000378:metabolism* / Q000494:pharmacology; D016466:CHO Cells; D002454:Cell Differentiation / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D016503:Drug Delivery Systems; D005109:Extracellular Matrix / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D011485:Protein Binding; D018000:Receptors, Peptide / Q000378:metabolism*; D020298:U937 Cells
D000942:Antigens, Bacterial; D000970:Antineoplastic Agents; D001427:Bacterial Toxins; D018000:Receptors, Peptide; C030325:anthrax toxin; C070309:anthrax toxin receptors