Axonal transport of monoclonal antibodies.
Three monoclonal antibodies against rat brain synaptosomes, produced by conventional hybridoma techniques, were screened for their ability to undergo uptake and axonal transport in vivo. Injections of ascitic fluid or of purified immunoglobulin G (IgG) were made into the vitreal chamber of the eye in anesthetized rats to test for anterograde transport in retinal afferents to the contralateral superior colliculus. Retrograde transport by facial nucleus motoneurons was evaluated after injections of antibody into the mystatial vibrissal skin and musculature. Transported immunoglobulins were localized in tissue sections using a modification of the peroxidase-antiperoxidase technique. One monoclonal antibody, S-2C10, was found to undergo anterograde transport in retinal ganglion cells and retrograde axonal transport in facial motoneurons. Transported immunoglobulins were detectable even after injections of dilute antibody solution (0.01-0.05% IgG), and the uptake-transport process for this antibody appeared saturable. Two other antibodies tested, S-4E9 and S-1G10, exhibited the ability to undergo retrograde transport, but only after injections at relatively high antibody concentrations (greater than or equal to 1.0% IgG). Neither of these antibodies was shown to undergo anterograde transport. Following retrograde transport in motoneurons, the S-2C10 antibody was localized in neuronal perikarya, proximal dendrites, and the adjacent neuropil of the facial motor nucleus. In contrast, the S-4E9 and S-1G10 antibodies were localized in punctate granules within neuronal cell somata following transport. The findings suggest that the uptake-transport process for the S-2C10 antibody is mediated by adsorptive endocytosis following binding of the antibody to a plasma membrane component (or components) present in somadendritic and nerve terminal membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
Ritchie
T C
TC
Fabian
R H
RH
Choate
J V
JV
Coulter
J D
JD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D001370:Axonal Transport; D002462:Cell Membrane / Q000378:metabolism; D004705:Endocytosis; D007124:Immunoenzyme Techniques; D009046:Motor Neurons / Q000378:metabolism; D009434:Neural Pathways / Q000378:metabolism; D051381:Rats; D013477:Superior Colliculi / Q000378:metabolism; D013574:Synaptosomes / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal