Even moderate cigarette smoking influences the pattern of circulating monocytes and the concentration of sICAM-1

doi:10.1016/S0034-5687(98)00098-X

Respiration Physiology

Volume 114, Issue 3, December 1998, Pages 269-275

Respiration Physiolo...

https://doi.org/10.1016/S0034-5687(98)00098-X Get rights and content

Abstract

The pattern of circulating monocyte subtypes and the concentration of the soluble intercellular adhesion molecule-1 (ICAM-1) were compared in middle-aged female moderate smokers and lifetime non-smokers. Total leukocyte and monocyte counts were higher in smokers. The pattern of circulating monocytes of smokers was changed toward lower absolute counts of activated (CD16+/CD64+) monocytes and (CD16+/CD14+) monocyte-macrophages and higher counts of nonactivated monocytes. The serum concentration of soluble ICAM-1 was significantly higher in smokers than in non-smokers. It is supposed that even moderate cigarette smoking leads to an activation of the circulating monocytes and their increased adhesion to the endothelium.

Introduction

In women, the cardiovascular risk increases dramatically after menopause. Menopause as a marker for the end of women‘s natural protection against coronary heart disease and aging are among the non-modifiable risk factors of atherosclerosis, while cigarette smoking, overweight or physical inactivity belong to the modifiable cardiovascular risk factors.

Cigarette smoking is a strong independent cardiovascular risk factor, associated with a chronic inflammatory process. In male severe smokers Targher et al. (1996) observed significant higher absolute and relative counts of circulating monocytes. Cigarette smoking may contribute to the development of atherosclerosis increasing the activation of circulating monocytes as well as their aggregation and adhesion to the endothelium. The adhesion of circulating leukocytes (monocytes) to the endothelium and their recruitment into the vessel wall are the earliest detectable events in the formation of atherosclerotic plaques (Fagged et al., 1984). The pool of circulating monocytes consists of different subpopulations which are discriminated by the expression of low (CD16) and high affinity (CD64) Fc receptors, the lipopolysaccharid (LPS) receptor (CD14) and the pan myeloid cell marker (CD33) (Rothe et al., 1996). Systemic abnormalities in the monocyte-macrophage subpopulation pattern may play a role in the atherogenesis (Rothe et al., 1996). The adhesion and the transendothelial migration of the circulating monocytes are mediated by several membrane-bound adhesion molecules of the integrin family. The intercellular adhesion molecule 1 (ICAM-1) represents their endothelial counterpart. ICAM-1 (CD54) is expressed by endothelial cell in response to inflammatory cytokines and binds to the receptors placed on monocytes (CD43),(CD11b). The serum concentration of the soluble ICAM-1 is a good surrogate marker for the cellular expression of this adhesion molecule.

The aim of the present study was to assess whether even moderate cigarette smoking in middle-aged women alters the pattern of circulating monocytes and/or modifies their adhesion to the endothelium.

Section snippets

Design

The subsample of 387 middle-aged women selected for this Public health study ¹ were participants of the DRECAN study². Among them were 33 women who smoked regular during the last 6 years (10 women<10 cigarettes/day, five women 10–20 cigarettes/day). The control

Results

Within normal ranges, the haematological parameters haemoglobin and haematokrit tend to higher values in smokers than in non-smokers. Mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH) are significantly higher in smokers. Total leukocyte counts are within the normal range (3.8–9.8 Gpt/l) in both groups, but the mean total leukocyte count is significantly higher in smokers than in non-smokers (Table 2). The percentage distribution of monocytes, neutrophiles and lymphocytes is

Discussion

Cigarette smoking was clearly linked with increased evidence of atherosclerosis and cardiovascular diseases. Cigarette smoking and hypercholesterolaemia as cardiovascular risk factors were associated with impaired endothelial function. The pathogenesis of atherosclerosis was characterized by an increased adhesion of monocytes to the endothelium. Huang et al. (1996) proposed that hypercholesterolaemia in men as well as in women has a strong peripheral monocyte-reducing effect due to direct

Acknowledgements

Authors thank the staff of the heamatological laboratory for their excellent realization of the flow cytometric analyses. This work was supported by a grant (DLR 01EG9410) by the Bundesministerium für Bildung und ForschungPublic Health Forschungsverbund Sachsen A5. Psychosoziale Ressourcen und kardiovaskuläres Risiko bei Frauen im mittleren Lebensalter.

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Citation Excerpt :
It has been demonstrated that smoking is associated with vascular endothelial inflammation and damages the epithelial junctions making them more permeable [20]. Even moderate cigarette smoking influences the plasma concentrations of cell adhesion molecules like e.g. sICAM-1 [21]. Smoking cessation has been shown to be a highly effective measure to lower sICAM-1 [9,22,23].
Endothelial dysfunction precedes atherosclerosis and smoking is a well-known risk factor for the development of endothelial dysfunction. The aim of our study was to analyse the effect of smoking on circulating markers of endothelial function and to investigate whether such effects have an influence on the potential use of these markers to estimate cardiovascular risk.
Stratified for smoking, levels of sE-/sP-/sL-selectin, von Willebrand (vWF), sICAM-1 and sVCAM-1, their association with mortality using Cox regression, and their accuracy of risk prediction using area-under-the-ROC-curve and net-reclassification-index were analysed in 1926 participants from the Ludwigshafen Risk and Cardiovascular Health (LURIC) – a prospective case-control study in patients who underwent coronary angiography with a median mortality follow-up of 10.6 years.
In smokers, higher concentrations of sICAM-1, sE-selectin sP-selectin, but lower concentrations of sL-selectin and sVCAM-1, were detected compared to never-smokers. A direct association with mortality was found for levels of sICAM-1, sVCAM-1 and vWF regardless of smoking. Low sL-selectin levels were inversely associated with mortality in heavy and light smokers, with hazard ratios of 0.72 and 0.67 per 1-SD increase, adjusted for cardiovascular risk factors. Adding sL-selectin to a model based on traditional risk factors significantly improved AUC from 0.725 to 0.752 (p = 0.034) with an NRI of 43% (16.9%–62.3%).
Smoking alters the concentration of circulating markers of endothelial function. sL-selectin is decreased in smokers, inversely associated with risk, and could be a useful marker to improve risk prediction.
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Cigarette smoking causes cardiovascular diseases. Heating tobacco instead of burning it reduces the amount of toxic compounds in the aerosol and may exert a reduced impact on health compared with cigarette smoke. Aqueous extract from the aerosol of a potential modified risk tobacco product, the Carbon Heated Tobacco Product (CHTP) 1.2, was compared in vitro with aqueous extract from the smoke of a 3R4F reference cigarette for its impact on the adhesion of monocytic cells to artery endothelial cells. Human coronary artery endothelial cells (HCAEC) were treated for 4 h with conditioned media from human monocytic Mono Mac 6 (MM6) cells exposed to CHTP1.2 or 3R4F extracts for 2 h or directly with those extracts freshly generated. In vitro monocyte-endothelial cell adhesion was measured concomitantly with inflammatory, oxidative stress, cytotoxicity, and death markers. Furthermore, transcriptomics analyses enabled to quantify the level of perturbation in HCAECs, and provide biological interpretation for the underlying molecular changes following exposure to 3R4F or CHTP1.2 extract. Our systems toxicology study demonstrated that approximately 10–15-fold higher concentrations of the CHTP 1.2 aerosol extract were needed to elicit similar effects as the 3R4F smoke extract on cardiovascular disease-relevant inflammation and cytotoxicity-related mechanisms and markers investigated in vitro.
Suitability of biomarkers of biological effects (BOBEs) for assessing the likelihood of reducing the tobacco related disease risk by new and innovative tobacco products: A literature review
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It is involved in the major smoking-related diseases such as CVD, respiratory diseases and also cancer (Brownawell, 2007; US Department of Health and Human Services, 2010). In Table S5, 32 studies, many of which studied large populations of S, NS and Ex, are briefly summarized and evaluated (Table S6) (Bakhru and Erlinger, 2005; Bazzano et al., 2003; Bergmann et al., 1998; Blann et al., 1998; Bolliger et al., 2002; Eliasson et al., 2001; Frohlich et al., 2003; Frost-Pineda et al., 2011; Hammett et al., 2007; Haswell et al., 2014; Iso et al., 1996; Kaptoge et al., 2007; Kawada, 2015; Krobot et al., 1992; Lavi et al., 2007; Liu et al., 2011; Ludicke et al., 2015; Martin Leroy et al., 2012; Miller et al., 2003; MINAMI et al., 2002; Nordskog et al., 2015; Panagiotakos et al., 2004; Rennard et al., 2006; Roethig et al., 2008; Shepperd et al., 2015; Tuut and Hense, 2001; van Dijk et al., 2013; Wannamethee et al., 2005; Woodward et al., 1999; Yarnell et al., 2000; Yasue et al., 2006; Zedler et al., 2006). On average, S had by 7% elevated plasma fibrinogen concentrations (25 studies, 18 studies showed a significant difference between S and NS).
The health risk of tobacco smoking can best be avoided or reduced by not taking up or quitting the habit. The use of new and innovative tobacco (NTPs, e.g. electronic cigarettes) can either be an aid for smoking cessation or, for those who are not able or willing to quit, an alternative for smoking conventional tobacco products. Before the use of an NTP can be regarded as an effective approach in tobacco harm reduction (THR), the implicated risk has to be evaluated by suitable toxicological methods such as the analysis of the chemical composition as well as assessment of detrimental effects in animal and in vitro studies. In human (clinical) studies, the NTP-related exposure to toxicants and early biological effects can be assessed by the determination of suitable biomarkers. In this review, the suitability of established and newly developed biomarkers of biological effect (BOBEs) for the indicated purpose is evaluated according to five criteria, including the association to diseases, reported difference in BOBE levels between smokers and non-smokers, dose-response relationships, reversibility and kinetics after smoking cessation. Furthermore, the effect size and the resulting sample size required in clinical studies were estimated and considered in the BOBE evaluation process. It is concluded that the rating process presented is useful for selecting BOBEs suitable for risk evaluation of NTPs in clinical and other human studies.
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Intercellular adhesion molecule-1 (ICAM-1) permits leukocyte-endothelial adhesion and transmigration during inflammation. Membrane-bound ICAM-1 knockout mice have been used to understand this molecule’s role in wound-healing, but expressed spliced isoforms of ICAM-1 that may have impacted results. We aimed to characterize wound-healing in an ICAM-1 null model devoid of all ICAM-1 isoforms.
Full-thickness 8-mm wounds were created on C57/BL6 wild-type (n = 24) and ICAM-1 null (n = 24) mice. Wound area was calculated using daily photographs. Histologic samples were harvested on postoperative Days 1, 3, 7, and 14. Wound margins were evaluated for mRNA expression of 13 inflammatory cytokines. A separate group of wild-type and ICAM-1 null mice (n = 24) received full-thickness incisions with tensiometry measured at Day 14. Separately, complete blood counts were measured in unwounded wild-type (n = 4) and ICAM-1 null mice (n = 4).
Wound-closure was significantly delayed in ICAM-1 null mice through Day 7 by gross and histologic measurement. mRNA expression of VEGF-A was increased in ICAM-1 null mice on Day 3, although no increase in VEGF-A was observed in the wound bed by immunohistochemistry. ICAM-1 null wounds demonstrated higher stiffness by tensiometry on Day 14 compared to the wild-type (1880 ± 926 kPa versus 478 ± 117 kPa; P < 0.01), and had higher counts of white blood cells (10,009 versus 5720 cells/μL, P < 0.05), neutrophils (2130 versus 630 cells/μL, P < 0.01), and lymphocytes (7130 versus 4,740 cells/μL, P < 0.05).
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Citation Excerpt :
The atherosclerotic process is initiated by the adhesion of activated monocytes to the impaired endothelium, which is followed by monocyte migration into the subendothelium, differentiation to macrophages, and subsequent formation of foam cells [9]. Several studies have shown that cigarette smoking increases the plasma levels of intercellular adhesion molecule-1 (ICAM-1), which is a marker of endothelial dysfunction [10–12]. A study also showed that cigarette smoking induces the expression of adhesion molecules, such as CD11b, on the surface of monocytes and causes the adhesion of these monocytes to endothelial cells [9], which may initiate the process of atherosclerosis.
Circulating adiponectin levels in cigarette smokers are lower than those in nonsmokers. We have previously shown that adiponectin is expressed in human monocytes. The aim of this study was to further investigate the effect of smoking on adiponectin expression in peripheral blood mononuclear cells (PBMCs).
A group of 77 cigarette smokers and 51 nonsmokers were consecutively enrolled in this study. The participants’ body weight, blood pressure, and metabolic parameters, including plasma glucose and plasma adiponectin levels, were recorded. The RNA from the PBMCs was assessed with real-time polymerase chain reaction (PCR) to determine the levels of adiponectin mRNA.
Of the 77 smokers, 67 (87.0%) were male. Their mean (standard deviation) age was 43.17 (11.47) years, and they smoked 24.56 (12.53) cigarettes/day. The duration of smoking was 23.73 (11.69) years. Both circulating adiponectin levels (p = 0.0262) and adiponectin mRNA levels in PBMCs (p < 0.0001) of smokers were significantly lower than those in nonsmokers. Both circulating adiponectin levels and adiponectin mRNA levels were negatively correlated with the number of cigarettes smoked per day (p < 0.01). In multiple linear regression analysis, smoking was an independent factor affecting adiponectin mRNA expression in PBMCs (p < 0.0001).
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That circulating soluble form of intercellular adhesion molecule-1 (sICAM-1) is associated with an increased risk for coronary artery disease is well recognized. However, information is scant regarding the distribution and cardiovascular (CV) risk correlates of sICAM-1 in asymptomatic young adults.
Plasma sICAM-1 was measured in 1,184 black and white persons in the Bogalusa Heart Study cohort (70% white, 43% male), aged 24 to 44 years. CV risk was assessed in terms of CV risk factors, status of parental CV disease, and composite carotid intima-media thickness (IMT).
sICAM-1 levels displayed race difference (whites > blacks, p < 0.0001), but no sex difference. In multivariate analysis including age, race, sex, smoking status, waist circumference, mean arterial pressure, low- and high-density lipoprotein (LDL and HDL) cholesterols, triglycerides, insulin resistance index, C-reactive protein (CRP), and adiponectin, the significant predictors of sICAM-1, in order of entry, were race (white > black), smoking, CRP, and waist circumference. Furthermore, there was a smoking by waist circumference interaction in that smoking attenuated the magnitude of correlation between waist circumference and sICAM-1. Levels of sICAM-1 adjusted for age, race, sex, and smoking increased with number of metabolic syndrome components (p for trend < 0.01); positive family history of CV disease (p < 0.05); and increased in composite carotid IMT specific for age, race, and sex (p for trend < 0.05).
These findings underscore the potential value of plasma sICAM-1 as an additional biomarker for CV risk among asymptomatic young adults.

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Even moderate cigarette smoking influences the pattern of circulating monocytes and the concentration of sICAM-1

Abstract

Introduction

Section snippets

Design

Results

Discussion

Acknowledgements

Cigarette smoking is associated with increased human monocyte adhesion to endothelial cells: reversibility with oral l-arginine but not vitamin C

J. Am. Coll. Cardiol.

Human monocyte characteristics are altered in hypercholesterolaemia

Atherosclerosis

Konzentration von Vitamin B12 und Folsäure bei Raucherinnen mittleren Lebensalters

Atemw. Lungenkrk.

Smoking and leukocyte counts: results of an epidemiological survey

Lancet

Association of plasma fibrinogen levels with coronary artery disease, smoking and inflammatory markers

Atherosclerosis

Cigarette smoking increases monocyte adherence to cultured endothelial cell monolayer

Biochem. Biophys. Res. Commun.

Monocyte adherence to endothelial cells in patients with atherosclerosis: relationships with risk factors

Eur. J. Clin. Invest.

Studies of hypercholesterolemia in the nonhuman pronate. 1. Changes that lead to the fatty streak formation

Arteriosclerosis

The relationship of white blood cell count to other cardiovascular risk factors

Int. J. Epidemiol.

In hypercholesterolemia, lower peripheral monocyte count is unique among the major predictors of atherosclerosis

Arterioscler. Thromb. Vasc. Biol.

Lack of endogenous estrogens effects on circulating adhesion molecule ICAM-1

J. Endocrinol. Invest.