Nicotine increases human polymorphonuclear leukocytes chemotactic response —a possible additional mechanism of lung injury in cigarette smokers

Nowak, Dariusz; Ruta, U; Piasecka, G

doi:10.1016/s0232-1513(11)80218-5

Cited by 45 publications

(21 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The responsiveness of leukocytes and platelets to a variety of agonists might be increased by smoking or by nicotine/cotinine. Thus, smoking-or nicotine-activated leukocytes (Nowak et al 1990;Bridges et al 1993) and platelets (Rival et al 1987;Blache et al 1992;Nowak et al 1996) may be the origin of increased eicosanoid synthesis. Nicotine stimulates the release of catecholamines from the adrenal gland (Benowitz 1991) and the release of serotonin from gastrointestinal enterochromaffin cells (Racké and Schwörer 1992), which are thought to be the main source of platelet serotonin (Verbeuren 1989).…”

Section: Discussionmentioning

confidence: 99%

Effects of smoking cessation and nicotine substitution on systemic eicosanoid production in man

Saareks

Ylitalo

Alanko

et al. 2001

Naunyn-Schmiedeberg's Archives of Pharmacology

View full text Add to dashboard Cite

This study investigated the effects of smoking cessation with and without nicotine substitution on the excretion of major urinary metabolites of thromboxane A2 and prostacyclin, 11-dehydrothromboxane B2 and 2,3-dinor-6-ketoprostaglandin F1alpha, respectively, as well as on the excretion of leukotriene E4 in man. Urine samples were obtained from 20 healthy non-smoking controls and from 60 healthy smoking volunteers before, and 3, 7 and 14 days after smoking cessation. Fifteen smokers quit smoking without nicotine substitution, 15 used nicotine chewing gum and 30 used nicotine patches as a substitution therapy. Urinary thiocyanate as well as cotinine and trans-3'-hydroxycotinine excretions were used as compliance and nicotine substitution indicators. 11-Dehydrothromboxane B2, 2,3-dinor-6-ketoprostaglandin F1alpha and leukotriene E4 excretion was about two, three and five times higher in smokers than in controls, respectively. Three days after smoking cessation without nicotine substitution, 11-dehydrothromboxane B2 and 2,3-dinor-6-ketoprostaglandin F1alpha levels were lowered to 75% (P<0.01) and 80% (P<0.05) of the initial values, and after 14 days to 50% (P<0.01) and 60% (P<0.05), respectively. In 3 days leukotriene E4 excretion was dropped to 70% of the initial value (P<0.05), but no further decrease was observed during the study. In individuals using nicotine chewing gum or nicotine patches no significant changes were observed in the analytes during the 2-week follow-up. The increased systemic eicosanoid synthesis observed in smokers may be involved in the harmful cardiovascular effects of smoking. The fact that eicosanoid production remains at pre-cessation level in volunteers who quit smoking but use nicotine substitution may be involved in the risk of cardiovascular complications reported during nicotine replacement therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of smoking cessation and nicotine substitution on systemic eicosanoid production in man

Saareks

Ylitalo

Alanko

et al. 2001

Naunyn-Schmiedeberg's Archives of Pharmacology

View full text Add to dashboard Cite

show abstract

“…ACh and its congeners are chemotactic for KCs, neurons, and other cell types (2)(3)(4)(5)(6)(7)(8). To characterize the physiologic control of keratinocyte migration, we developed an in vitro model of skin epithelialization, termed the agarose gel keratinocyte outgrowth system (AGKOS) (9).…”

mentioning

confidence: 99%

The Ras/Raf-1/MEK1/ERK Signaling Pathway Coupled to Integrin Expression Mediates Cholinergic Regulation of Keratinocyte Directional Migration

Chernyavsky

Arredondo

Karlsson

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

The physiologic mechanisms that determine directionality of lateral migration are a subject of intense research. Galvanotropism in a direct current (DC) electric field represents a natural model of cell re-orientation toward the direction of future migration. Keratinocyte migration is regulated through both the nicotinic and muscarinic classes of acetylcholine (ACh) receptors. We sought to identify the signaling pathway mediating the cholinergic regulation of chemotaxis and galvanotropism. The pharmacologic and molecular modifiers of the Ras/Raf-1/MEK1/ERK signaling pathway altered both chemotaxis toward choline and galvanotropism toward the cathode in a similar way, indicating that the same signaling steps were involved. The galvanotropism was abrogated due to inhibition of ACh production by hemicholinium-3 and restored by exogenously added carbachol. The concentration gradients of ACh and choline toward the cathode in a DC field were established by highperformance liquid chromatographic measurements. This suggested that keratinocyte galvanotaxis is, in effect, chemotaxis toward the concentration gradient of ACh, which it creates in a DC field due to its highly positive charge. A time-course immunofluorescence study of the membrane redistribution of ACh receptors in keratinocytes exposed to a DC field revealed rapid relocation to and clustering at the leading edge of ␣7 nicotinic and M 1 muscarinic receptors. Their inactivation with selective antagonists or small interfering RNAs inhibited galvanotropism, which could be prevented by transfecting the cells with constitutively active MEK1. The end-point effect of the cooperative signaling downstream from ␣7 and M 1 through the MEK1/ERK was an up-regulated expression of ␣ 2 and ␣ 3 integrins, as judged from the results of real-time PCR and quantitative immunoblotting. Thus, ␣7 works together with M 1 to orient a keratinocyte toward direction of its future migration. Both ␣7 and M 1 apparently engage the Ras/Raf/MEK/ERK pathway to up-regulate expression of the "sedentary" integrins required for stabilization of the lamellipodium at the keratinocyte leading edge. Human epidermal keratinocytes (KCs)2 can synthesize and secrete acetylcholine (ACh) and use it as a local hormone for an autocrine and paracrine control of their vital functions, including motility (1). ACh and its congeners are chemotactic for KCs, neurons, and other cell types (2-8). To characterize the physiologic control of keratinocyte migration, we developed an in vitro model of skin epithelialization, termed the agarose gel keratinocyte outgrowth system (AGKOS) (9). Using AGKOS, we have demonstrated that activation of the keratinocyte nicotinic ACh receptors (nAChRs) comprised by ␣7 subunits exhibit reciprocal effects on cell motility by stimulating directional (chemotaxis) and inhibiting random (chemokinesis) migration and that ACh-gated ion channels containing ␣3 subunit stimulate chemokinesis of KCs (8).More recently, ␣7 nAChR has been shown to mediate chemotaxis of vascular smooth muscle cells to...

show abstract

“…receptors (nAChRs) is chemotactic for neutrophils (Nowak et al, 1990;Totti et al, 1984). Choline, a selective agonist of α7 nAChR (Alkondon et al, 1997;Papke et al, 1996), is a ligand for chemosensation and chemotaxis (Yassin et al, 2001).…”

mentioning

confidence: 99%

Differential regulation of keratinocyte chemokinesis and chemotaxis through distinct nicotinic receptor subtypes

Chernyavsky

Arredondo

Marubio

et al. 2004

Journal of Cell Science

View full text Add to dashboard Cite

Nicotinergic agents can act as both chemokines and chemoattractants for cell migration. Epidermal keratinocytes both synthesize acetylcholine and use it as a paracrine and autocrine regulator of cell motility. To gain a mechanistic insight into nicotinergic control of keratinocyte motility, we determined types of nicotinic acetylcholine receptors and signaling pathways regulating keratinocyte chemokinesis and chemotaxis, using respective modifications of the agarose gel keratinocyte outgrowth assay. Random migration of keratinocytes was significantly (P<0.05) inhibited by hemicholinum-3, a metabolic inhibitor of acetylcholine synthesis, as well as by the α-conotoxins MII and AuIB, preferentially blocking α3-containing nicotinic acetylcholine receptors. The use of antisense oligonucleotides specific for nicotinic-acetylcholine-receptor subunits and knockout mice demonstrated pivotal role for the α3β2 channel in mediating acetylcholine-dependent chemokinesis. Signaling pathways downstream of α3β2 included activation of the protein-kinase-C isoform δ and RhoA-dependent events. The nicotinergic chemotaxis of keratinocytes was most pronounced towards the concentration gradient of choline, a potent agonist of α7 nicotinic acetylcholine receptor. The α7-preferring antagonist α-bungarotoxin significantly (P<0.05) diminished keratinocyte chemotaxis, further suggesting a central role for the α7 nicotinic acetylcholine receptor. This hypothesis was confirmed in experiments with anti-α7 antisense oligonucleotides and α7-knockout mice. The signaling pathway mediating α7-dependent keratinocyte chemotaxis included intracellular calcium, activation of calcium/calmodulin-dependent protein-kinase II, conventional isoforms of protein-kinase C, phosphatidylinositol-3-kinase and engagement of Rac/Cdc42. Redistribution of α7 immunoreactivity to the leading edge of keratinocytes upon exposure to a chemoattractant preceded crescent shape formation and directional migration. Application of high-resolution deconvolution microscopy demonstrated that, on the cell membrane of keratinocytes, the nicotinic acetylcholine receptor subunits localize with the integrin β1. The obtained results demonstrate for the first time that α3 and α7 nicotinic acetylcholine receptors regulate keratinocyte chemokinesis and chemotaxis, respectively, and identify signaling pathways mediating these functions, which has clinical implications for wound healing and control of cancer metastases.

show abstract

Nicotine increases human polymorphonuclear leukocytes chemotactic response —a possible additional mechanism of lung injury in cigarette smokers

Cited by 45 publications

References 15 publications

Effects of smoking cessation and nicotine substitution on systemic eicosanoid production in man

Effects of smoking cessation and nicotine substitution on systemic eicosanoid production in man

The Ras/Raf-1/MEK1/ERK Signaling Pathway Coupled to Integrin Expression Mediates Cholinergic Regulation of Keratinocyte Directional Migration

Differential regulation of keratinocyte chemokinesis and chemotaxis through distinct nicotinic receptor subtypes

Contact Info

Product

Resources

About