Effects of taxol on microtubule organization in mouse splenic lymphocytes and on response to mitogenic stimulation.
We have used immunofluorescence staining with antibodies to tubulin and electron microscopy to examine the effects of microtubule assembly-promoting drug taxol on the organization of microtubules in unstimulated and in mitogen stimulated mouse splenic lymphocytes. A 4-h exposure to 10 microM taxol of unstimulated or stimulated cells results in an extensive reorganization of the microtubule system to form one to a few large bundles of microtubules which extend from the centrosome. Concomitantly, the centrosome is displaced from the normal position near the nucleus to a position near the plasma membrane. The Golgi apparatus is not disrupted by this treatment and also appears to be displaced in association with the centrosome. We then examined the capacity of lymphocytes with taxol-reorganized microtubules to respond to stimulation by the mitogen concanavalin A. The taxol-induced reorganization of microtubules has no effect on the increase in cell size (blastogenesis), the changes in structure of the nucleus and cytoplasm, or on the DNA replication that occurs in response to mitogen. The stimulated cells, however, do not proliferate and appear to accumulate in mitosis with the appearance of multiple asters. We conclude that all of the major events of mitogenic stimulation up to the first mitosis can occur in the presence of a highly reorganized microtubule system. Our results suggest that taxol will be a useful drug in determining those lymphocyte functions that are dependent on the presence of normal microtubule organization.
Brown
D L
DL
Little
J E
JE
Chaly
N
N
Schweitzer
I
I
Paulin-Levasseur
M
M
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure*; D017239:Paclitaxel; D013154:Spleen
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel