The role of calcium in neutrophil migration: The effect of calcium and calcium-antagonists in electroporated neutrophils

Elferink, J. G. R.; Boonen, G. J. J. C.; Koster, Ben M. de

doi:10.1016/0006-291x(92)91812-5

Cited by 22 publications

(6 citation statements)

References 20 publications

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“…5). It must be pointed out that organic Ca 2ϩ channel blockers have been reported to inhibit various PMN functions elicited by FMLP, bacteria, or latex in vitro and ex vivo (3,13,25,26,53). According to Jaconi et al (22), the mechanism of calcium influx in stimulated PMNs does not appear to involve voltage-operated, receptor-operated, or second messenger-operated Ca 2ϩ channels but correlates with the filling state of intracellular Ca 2ϩ stores and is referred to as capacitative Ca 2ϩ influx (42).…”

Section: Discussionmentioning

confidence: 99%

“…Various investigators have observed that only relatively high concentrations of verapamil or nifedipine, two Ca 2ϩ antagonists, alter neutrophil function, whereas these drugs are inhibitory at 10 5 -fold lower concentrations in electroporated neutrophils (13), suggesting that Ca 2ϩ channels in the PMN cytoplasmic membrane are not sensitive to these inhibitors. In keeping with these data, we observed that nifedipine (100 to 500 M) did not inhibit macrolide uptake over a 60-min incubation period (data not shown).…”

Section: Cellular Location Of Macrolidesmentioning

confidence: 99%

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Role of extracellular calcium in in vitro uptake and intraphagocytic location of macrolides

Mtairag

Abdelghaffar

Douhet

et al. 1995

Antimicrob Agents Chemother

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We compared the uptakes and intracellular locations of four 14-membered-ring macrolides (roxithromycin, dirithromycin, erythromycin, and erythromycylamine) in human polymorphonuclear neutrophils (PMNs) in vitro. Intracellular location was assessed by cell fractionation and uptake kinetics in cytoplasts (granule-poor PMNs). Trapping of dirithromycin within PMN granules (up to 80% at 30 min) was significantly more marked than the intracellular trapping of the other drugs (erythromycylamine, 45% ؎ 5.1%; erythromycin, 42% ؎ 3.7%; roxithromycin, 35% ؎ 3.0%). A new finding was that, in the absence of extracellular calcium, the uptakes of all of the macrolides by PMNs and cytoplasts were significantly impaired, by about 50% (PMN) and 90% (cytoplasts). Furthermore, inorganic Ca 2؉ channel blockers inhibited macrolide uptake in a concentrationdependent manner, with 50% inhibitory concentrations of 1.6 to 2.0 mM and 29 to 35 M, respectively, for Ni The organic Ca 2؉ channel blocker nifedipine had no effect on macrolide uptake, whereas verapamil inhibited it in a time-and concentration-dependent manner. These data show the importance of extracellular Ca 2؉ in macrolide uptake by phagocytes and suggest a link with Ca 2؉ channels or a Ca 2؉ channel-operated mechanism.Infections caused by organisms which survive and multiply within host cells, such as Legionella spp., Chlamydia spp., and Mycobacteria spp., are difficult to cure, partly because of the intracellular locations of these pathogens, which are protected from the antimicrobial activities of non-cell-penetrating agents (20). However, the abilities of antibiotics to enter and concentrate within host cells, generally estimated from the intracellular concentration-to-extracellular concentration ratio, may not actually reflect their overall intracellular bactericidal activities (17). Another factor of importance is the respective intracellular locations of the drug and the pathogen. Possible interactions between the drug and host cell factors (inactivation, binding, synergy) may also result from the particular location of the drug. In addition, intracellular accumulation of antibacterial agents or the mechanism used for this cellular transport may in turn affect host cell metabolism and functions, ultimately modifying the overall course of infectious diseases. Among those cell-penetrating agents, macrolide antibiotics have been much studied (14,27). Many publications examine their intracellular (particularly intraphagocytic) accumulation (for a review, see reference 29) and their possible interference with phagocyte activities (for a review, see reference 28). Despite abundant data, the mechanism underlying macrolide uptake by host cells is poorly understood. Various hypotheses have been put forward. These hypotheses involve liposolubility and active transport systems, particularly those used by nucleosides (18, 21). A likely mechanism for their intracellular accumulation involves the weakly basic nature of macrolides and the possibility of trapping by protonation within ...

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Section: Discussionmentioning

confidence: 99%

Section: Cellular Location Of Macrolidesmentioning

confidence: 99%

Role of extracellular calcium in in vitro uptake and intraphagocytic location of macrolides

Mtairag

Abdelghaffar

Douhet

et al. 1995

Antimicrob Agents Chemother

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“…Several studies have shown that phagocytic functions are impaired by calcium channel blockers in vitro [12][13][14]. Several studies have shown that phagocytic functions are impaired by calcium channel blockers in vitro [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Inhibited neutrophil functions in patients treated with nifedipine but not with verapamil or diltiazem

Lévy

Nagauker-Shriker²,

Schlaeffer

1996

Eur J Clin Investigation

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Neutrophil functions were studied in patients receiving calcium channel blockers: nifedipine, diltiazem or verapamil. Neutrophils from patients treated with nifedipine showed a significantly lower superoxide generation stimulated by phorbol myristate acetate (PMA) (50 ng mL-1), opsonized zymosan (1 mg mL-1) or formyl-methionyl-leucylphenylalanine (FMLP) (10(-7) M), whereas superoxide generation by neutrophils of patients receiving diltiazem or verapamil showed only a slight and insignificant reduction compared with controls. Similarly, chemotaxis towards 10(-7) M FMLP and phagocytosis were significantly lower in patients receiving nifedipine compared with controls and were only slightly reduced in patients receiving diltiazem or verapamil. Nifedipine was the most efficient drug in inhibiting the rise in intracellular calcium ion concentration ([Ca2+]i) when added in vitro and in neutrophils of patients receiving this drug, whereas verapamil had no significant effect. The correlation between the inhibitory effect of nifedipine on neutrophil function and the elevation of [Ca2+]i suggests that nifedipine inhibits neutrophil functions through its effect on [Ca2+]i. However, it is not the sole mechanism as superoxide generation induced by PMA, an agent that does not induce a rise in [Ca2+]i, is also inhibited. The unique effect of nifedipine in reducing neutrophil functions in vivo suggests its clinical implications concerning response to acute ischaemic myocardial events.

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“…On the other hand, these inflammatory processes are mediated by impairment in calcium homeostasis; there has been interest in the potential role of CCBs as anti-inflammatory agents (Henry, 1985;Henry and Bentley, 1989). Many studies show the important role of calcium ions on the synthesis and release of these inflammation mediators, which are present in the pathogenesis of carrageenan induced inflammation (Elferink et al, 1992;Leslie, 1997;Carnevale and Cathcart, 2001;El-Bizri et al, 2003). The anti-inflammatory mechanisms of CCB can be summarized as inhibition of the synthesis of the products of cyclooxygenase and lipoxygenase as non-steroidal anti-inflammatory drugs (NSAIDs), prevention of aggregation, adhesion and chemotaxis of neutrophils, blockage of the release of lysosomal enzymes and toxic oxygen radicals, and uncoupling of oxidative phosphorylation (Martinez et al, 1999;Sirmagul et al, 2004;Kouoh et al, 2006).…”

Section: Discussionmentioning

confidence: 93%

Effects of calcium channel blockers on hyaluronidase-induced capillary vascular permeability

2008

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Inflammation and increased capillary permeability is a significant aspect of the pathogenesis of many diseases including atherosclerosis. L-type calcium channel blockers (CCB) are commonly used as cardiovascular drugs. Amlodipine, lacidipine, and nicardipine were evaluated for anti-inflammatory activity on the paw oedema produced by carrageenan. The effect of these drugs was compared with the activity of indomethacin. Their effects on vascular permeability were also tested by hyaluronidase-induced capillary permeability. In our animal experiments, amlodipine decreased the carrageenan-induced paw oedema at doses of 1, 3, and 6 mg kg(-1) by 27.3%, 43.7%, and 67.3% four hour after carrageenan administration; the same doses of lacidipine and nicardipine decreased paw oedema by 37.1%, 55.6%, 76.4%, 11.2%, 31.0%, 91%; and indomethacin decreased oedema by 38.2% at a dose of 6 mg kg(-1). Lacidipine significantly inhibited the hyaluronidase-induced increase in capillary permeability at doses of 1, 3, and 6 mg kg(-1) compared with the control group. However, amlodipine and nicardipine significantly inhibited the hyaluronidase-induced increase in capillary permeability at 3 and 6 mg kg(-1) doses. A 6 mg kg(-1) dose of indomethacin significantly decreased the capillary permeability which was increased by hyaluronidase. These results suggest that CCBs can be efficient anti-inflammatories, and can also significantly decrease capillary permeability.

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The role of calcium in neutrophil migration: The effect of calcium and calcium-antagonists in electroporated neutrophils

Cited by 22 publications

References 20 publications

Role of extracellular calcium in in vitro uptake and intraphagocytic location of macrolides

Role of extracellular calcium in in vitro uptake and intraphagocytic location of macrolides

Inhibited neutrophil functions in patients treated with nifedipine but not with verapamil or diltiazem

Effects of calcium channel blockers on hyaluronidase-induced capillary vascular permeability

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