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Influence of a microtubule stabilizing agent on platelet structural physiology.

James G. White, Gundu H.R. Rao

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Abstract

Unstimulated blood platelets have a characteristic discoid form supported by a circumferential band of microtubules. After exposure to aggregating agents, platelets lose their lentiform shape and become irregularly convoluted, with many pseudopods. The changes in surface contour are associated with a process of internal transformation. Randomly dispersed granules are concentrated in cell centers and enclosed within tight-fitting rings of microtubules and microfilaments. The mechanism involved in the shift of circumferential microtubules into rings encircling clumped granules is uncertain. Recent studies have suggested that microtubules are disassembled shortly after stimulation and reassemble in new locations a few minutes later. Taxol, a microtubule stabilizing agent, has been used in the present study to evaluate the disassembly-reassembly hypothesis of internal transformation in activated platelets. Stabilization of microtubules by taxol did not injure platelet biochemistry or structure. Concentrations of taxol that protected platelet microtubules from dissociation by cold or vincristine did not inhibit platelet shape change, pseudopod formation, internal transformation, secretion, aggregation, or clot retraction. The number of microtubules wrapped around centrally clumped granules, present in pseudopods or spread through the cytoplasm, was equal to or greater than that found in untreated platelets following activation and aggregation. Though it is possible that microtubules dissolve in platelets following activation, the results of this study demonstrate that such an event is not essential for any aspect of the physiologic response of platelets in hemostasis.

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What this paper is about

Unstimulated blood platelets have a characteristic discoid form supported by a circumferential band of microtubules. After exposure to aggregating agents, platelets lose their lentiform shape and become irregularly convoluted, with many pseudopods. The changes in surface contour are associated with a process of internal transformation. Randomly dispersed granules are concentrated in cell centers and enclosed within tight-fitting rings of microtubules and microfilaments. The mechanism involved in the shift of circumferential microtubules into rings encircling clumped granules is uncertain. Recent studies have suggested that microtubules are disassembled shortly after stimulation and reassemble in new locations a few minutes later. Taxol, a microtubule stabilizing agent, has been used in the present study to evaluate the disassembly-reassembly hypothesis of internal transformation in activated platelets. Stabilization of microtubules by taxol did not injure platelet biochemistry or structure. Concentrations of taxol that protected platelet microtubules from dissociation by cold or vincristine did not inhibit platelet shape change, pseudopod formation, internal transformation, secretion, aggregation, or clot retraction. The number of microtubules wrapped around centrally clumped granules, present in pseudopods or spread through the cytoplasm, was equal to or greater than that found in untreated platelets following activation and aggregation. Though it is possible that microtubules dissolve in platelets following activation, the results of this study demonstrate that such an event is not essential for any aspect of the physiologic response of platelets in hemostasis.

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Available abstract

Unstimulated blood platelets have a characteristic discoid form supported by a circumferential band of microtubules. After exposure to aggregating agents, platelets lose their lentiform shape and become irregularly convoluted, with many pseudopods. The changes in surface contour are associated with a process of internal transformation. Randomly dispersed granules are concentrated in cell centers and enclosed within tight-fitting rings of microtubules and microfilaments. The mechanism involved in the shift of circumferential microtubules into rings encircling clumped granules is uncertain. Recent studies have suggested that microtubules are disassembled shortly after stimulation and reassemble in new locations a few minutes later. Taxol, a microtubule stabilizing agent, has been used in the present study to evaluate the disassembly-reassembly hypothesis of internal transformation in activated platelets. Stabilization of microtubules by taxol did not injure platelet biochemistry or structure. Concentrations of taxol that protected platelet microtubules from dissociation by cold or vincristine did not inhibit platelet shape change, pseudopod formation, internal transformation, secretion, aggregation, or clot retraction. The number of microtubules wrapped around centrally clumped granules, present in pseudopods or spread through the cytoplasm, was equal to or greater than that found in untreated platelets following activation and aggregation. Though it is possible that microtubules dissolve in platelets following activation, the results of this study demonstrate that such an event is not essential for any aspect of the physiologic response of platelets in hemostasis.

Key concepts: Pseudopodia, Microtubule, Platelet, Cytoplasm, Biophysics, Microfilament, Chemistry, Cell biology

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