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Stimulation of rabbit polymorphonuclear leukocyte locomotion by D-penicillamine
1Department of Medical Biochemistry, University of Leiden, The Netherlands.
Abstract:
Treatment of polymorphonuclear leukocytes (PMNs) with penicillamine has little effect on chemotaxis of the cells towards fMet-Leu-Phe. In the absence of fMet-Leu-Phe however, penicillamine has a strong effect on PMN locomotion. Penicillamine-induced enhancement of PMN migration is for an important part due to a chemokinetic effect, but there is also a chemotactic effect. Pretreatment of PMNs with membrane-impermeable sulfhydryl reagents has little effect on random locomotion, but completely abolishes the activating effect of penicillamine. This suggests that for the activating effect of penicillamine intact sulfhydryl groups on the outer surface of the PMN are required. Extracellular calcium is no absolute requirement for PMN migration, neither for random locomotion nor for the activating effect of penicillamine. Removal of intracellular Ca2+ with membrane-penetrating Ca2+-complexing agents strongly inhibit penicillamine-induced enhancement of PMN migration, underlining a role for intracellular calcium. Penicillamine causes an increase of cGMP level in PMNs. Though a simple relationship seems unlikely it is possible that the enhancement of PMN migration, and the increase of cGMP level by penicillamine are related processes.
Insights
Penicillamine enhances polymorphonuclear leukocyte (PMN) migration, acting as both a chemokinetic and chemotactic agent. This effect requires intact surface sulfhydryl groups and involves intracellular calcium, potentially linked to increased cGMP levels.
Area of Science:
- Immunology
- Cell Biology
Background:
- Polymorphonuclear leukocytes (PMNs) are crucial immune cells involved in inflammatory responses.
- Understanding factors that modulate PMN migration is vital for immune system research.
Purpose of the Study:
- To investigate the effects of penicillamine on PMN migration and elucidate the underlying mechanisms.
- To determine the role of cell surface sulfhydryl groups and intracellular calcium in penicillamine-induced PMN activation.
Main Methods:
- Treatment of PMNs with penicillamine.
- Assessing PMN chemotaxis and chemokinesis towards fMet-Leu-Phe.
- Utilizing sulfhydryl reagents and calcium chelators to probe molecular mechanisms.
- Measuring intracellular cyclic guanosine monophosphate (cGMP) levels.
Main Results:
- Penicillamine significantly enhances PMN locomotion in the absence of chemoattractants, exhibiting both chemokinetic and chemotactic properties.
- The activating effect of penicillamine is dependent on intact sulfhydryl groups on the PMN surface.
- Intracellular calcium, but not extracellular calcium, plays a critical role in penicillamine-induced PMN migration enhancement.
- Penicillamine treatment leads to an increase in intracellular cGMP levels within PMNs.
Conclusions:
- Penicillamine modulates PMN migration through mechanisms involving cell surface sulfhydryl groups and intracellular calcium signaling.
- The observed increase in cGMP levels may be associated with penicillamine's effects on PMN migration, although the direct relationship requires further investigation.