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Abstract:
The adherence of human polymorphonuclear leukocytes (PMN) to nylon fibers is inhibited in a dose-dependent fashion by exposure in vitro of these cells to either colchicine or VM-26, both of which agents prevent microtubule assembly. Mean adherence of human PMN was 48% +/- 2%, following treatment with 10(-5) M colchicine or 10(-4) M VM-26 it was reduced to 31% +/- 2% and 7%, respectively. Peritoneal PMN obtained from mice and mink with Chediak-Higashi syndrome (CHS) thought to have a microtubule-membrane disorder affecting the PMN had a mean adherence of 29% +/- 3% and 40% +/- 8% compared to control values of 46% +/- 5% and 73% +/- 8%, respectively, from the mice and mink. Both ascorbic acid and bethanechol, shown previously to enhance microtubule assembly in humans with CHS, normalized granulocyte adherence in PMN obtained from mice with CHS. Cyclic nucleotide levels were not altered by treatment of human PMN with colchicine, nor did they differ between normal and CHS animals. Thus it appears that the state of microtubule assembly may directly affect the properties of the PMN plasma membrane without requiring alterations of cyclic nucleotides as an intermediary.
Insights
Microtubule assembly directly impacts polymorphonuclear leukocyte (PMN) adherence to nylon fibers. Inhibiting microtubule assembly reduces PMN adherence, while enhancing it normalizes adherence in Chediak-Higashi syndrome.
Area of Science:
- Cell Biology
- Immunology
- Biochemistry
Background:
- Polymorphonuclear leukocytes (PMN) play a crucial role in immune responses.
- Microtubules are essential cytoskeletal components influencing cell function.
- Chediak-Higashi syndrome (CHS) is a genetic disorder characterized by impaired immune cell function, potentially linked to microtubule defects.
Purpose of the Study:
- To investigate the role of microtubule assembly in regulating PMN adherence.
- To determine if inhibiting microtubule assembly affects PMN adherence.
- To explore potential therapeutic interventions for CHS by targeting microtubule function.
Main Methods:
- In vitro treatment of human PMN with colchicine and VM-26 to inhibit microtubule assembly.
- Assessment of PMN adherence to nylon fibers following drug treatment.
- Analysis of peritoneal PMN adherence from normal and CHS mice and mink.
- Evaluation of the effects of ascorbic acid and bethanechol on PMN adherence in CHS models.
Main Results:
- Colchicine and VM-26 significantly reduced human PMN adherence in a dose-dependent manner.
- PMN from CHS mice and mink exhibited reduced adherence compared to controls.
- Ascorbic acid and bethanechol normalized granulocyte adherence in PMN from CHS mice.
- Cyclic nucleotide levels remained unchanged in treated human PMN and in CHS animals.
Conclusions:
- Microtubule assembly state directly influences PMN plasma membrane properties.
- Alterations in microtubule assembly affect PMN adherence independently of cyclic nucleotide levels.
- Targeting microtubule assembly may offer a therapeutic strategy for immune disorders like CHS.