Abstract
The pathology of atherosclerotic cardiovascular disease (ASCVD) has been characterized as an inflammatory response to vessel injury. The initial steps of this response involve mononuclear leukocyte (MNL) attachment and infiltration into the vessel wall. Leukocyte adhesion is potentiated by expression of cellular adhesion molecules. Vascular cell adhesion molecule-1 (VCAM) and intracellular adhesion molecule-1 (ICAM) are markers of cellular activation and have the ability to attach leukocytes to the endothelium, which is an initial event in the inflammatory response in the vessel wall. Human umbilical vein endothelial cells (HUVEC) were plated in endothelial growth medium (EGM) on plastic coverslips and grown until cells were 75% confluent. Free base nicotine (FBN) was diluted in EGM to a concentration of 10−8 M and added to experimental cells. At 3 hr, coverslips were removed and fixed. Immunohistochemical staining (IHCS) was performed using a monoclonal antibody to human ICAM and VCAM. Digital image analysis (DIA) was performed to quantify the expression of ICAM and VCAM. An intensity stain index (ISI) measuring area and intensity of stain/total cellular area was determined. Additional HUVEC grown in a similar manner were either exposed to 10−8 M FBN in EGM or EGM control for 4 hr, then were exposed to MNL suspension for 10 min. Coverslips were removed, rinsed, and fixed. Hematoxylin and eosin staining was performed and cells examined under light microscopy. Leukocyte number per high power field (HPF) was counted and compared to controls. Data were analyzed using analysis of variants (ANOVA) and Student’s t-test. Differences were considered significant if p < 0.05. ICAM and VCAM expression was absent in control cells. Nicotine exposure at 3 hr induced expression of VCAM (ISI = 30.85 ± 0.77) and to a lesser extent ICAM (ISI = 16.6 ± 1.39) (p < 0.001). MNL adhesion was markedly increased in cells exposed to nicotine (79.4 ± 16.9/HPF) when compared to control cells (1.8 ± 0.91/HPF) exposed to MNL (p < 0.01). These data show nicotine’s ability to activate HUVEC as evidenced by induction of ICAM and VCAM expression in vitro. The biological effects of these adhesion molecules are demonstrated by a marked increase in MNL adhesion to HUVEC as demonstrated by leukocyte adhesion assay (LAA). MNL adhesion and subsequent migration into the intima, if occurring in vivo, may be a vital step in the pathogenesis of ASCVD associated with nicotine exposure.
Similar content being viewed by others
References
R Ross (1993) ArticleTitleThe pathogenesis of atherosclerosis: a perspective for the 1990’s Nature 362 801–809 Occurrence Handle1:CAS:528:DyaK3sXktVGqu7c%3D Occurrence Handle8479518
G Albaugh B Kann L Strande P Vemulapalli C Hewitt JB Alexander (2001) ArticleTitleNicotine induces endothelial TNF-alpha expression, which mediates growth retardation in vitro J. Surg. Res. 99 381–384 Occurrence Handle10.1006/jsre.2001.6215 Occurrence Handle1:CAS:528:DC%2BD3MXlsVSjt7s%3D Occurrence Handle11469915
MA Gimbrone JN Topper (1999) Biology of the vessel wall endothelium KR Chen (Eds) Molecular Basis of Cardiovascular Disease WB Saunders Philadelphia 331–348
CJ Pepine (1998) ArticleTitleClinical implications of endothelial dysfunction Clin. Cardiol. 21 795–799 Occurrence Handle1:STN:280:DyaK1M%2Fkt1Kgsw%3D%3D Occurrence Handle9825190
AA Quyyumi (1998) ArticleTitleEndothelial function in health and disease: new insights into the genesis of cardiovascular disease Am. J. Med. 105 325–395 Occurrence Handle10.1016/S0002-9343(98)00209-5
MC Chia (1998) ArticleTitleThe role of adhesion molecules in atherosclerosis Crit. Res. Clin. Lab. Sci. 35 573–602 Occurrence Handle1:CAS:528:DyaK1MXltFensA%3D%3D
RS Cotran T Mayadasnorton (1998) ArticleTitleEndothelium, Leukocytes, and adhesion: endothelial adhesion molecules in health and disease Pathol. Biol. 46 164–170a Occurrence Handle1:CAS:528:DyaK1cXivFahsrw%3D Occurrence Handle9769911
M Navab SY Hama TB Nguyen AM Fogelman (1994) ArticleTitleMonocyte adhesion and Transmigration in atherosclerosis Coron. Artery Dis. 5 198–204 Occurrence Handle1:STN:280:ByuB2MfjsFE%3D Occurrence Handle8199733
J Meerschaert MB Furie (1995) ArticleTitleThe adhesion molecules used by monocytes for migration across Endothelium include CD11a/CD18, ligands on endothelium J. Immunol. 154 4099–4112 Occurrence Handle1:CAS:528:DyaK2MXkvFOru70%3D Occurrence Handle7535821
HM Dansky CB Barlow C Lominska et al. (2001) ArticleTitleAdhesion of monocytes to arterial endothelium and initiation of atherosclerosis are critically dependent on vascular cell adhesion molecule-1 gene dosage Arterioscler. Thromb. Vasc. Biol. 21 1662–1667 Occurrence Handle1:CAS:528:DC%2BD3MXnslGlsr8%3D Occurrence Handle11597942
M Hanyu N Kume T Ikeda M Minami T Kita M Komeda (2001) ArticleTitleVCAM-1 expression precedes macrophage infiltration into subendothelium of vein grafts interposed into carotid arteries in hypercholesterolemic rabbits—a potential role in vein graft atherosclerosis Atherosclerosis 158 313–319 Occurrence Handle10.1016/S0021-9150(01)00446-4 Occurrence Handle1:CAS:528:DC%2BD3MXnt1Whtb4%3D Occurrence Handle11583709
CG Kevil RP Patel DC Bullard (2001) ArticleTitleEssential role of ICAM-1 in mediating monocyte adhesion to aortic endothelial cells Am. J. Physiol. 281 1442–1447
Y Shen V Rattan C Sultana VK Kalra (1996) ArticleTitleCigarette smoke condensate-induced adhesion molecule expression and transedothelial migration of monocytes Am. J. Physiol. 270 1624–1633
S Zhang I Day S Ye (2001) ArticleTitleNicotine-Induced changes in gene expression by human coronary artery endothelial cells Atherosclerosis 154 277–283 Occurrence Handle10.1016/S0021-9150(00)00475-5 Occurrence Handle1:CAS:528:DC%2BD3MXpt12nsQ%3D%3D Occurrence Handle11166759
JG Hardman LE Limbard (Eds) (1996) Goodman and Gillmans Pharmocologic Basis of Therapeutics EditionNumber9th edition McGraw Hill Philadelphia 191–193
H Chen C Liu S Sun Y Mei E Tong (2001) ArticleTitleCytokine-induced cell surface expression of adhesion molecules in vascular endothelial cells in vitro J. Tongji Med. Univ. 1 68–71
MP Bevilacqua JS Pober ME Wheeler RS Cotran MA Gimbrone SuffixJr (1985) ArticleTitleInterleukin-1 activation of vascular endothelium. Effects on procoagulant activity and leukocyte adhesion Am. J. Pathol. 121 394–403 Occurrence Handle1:CAS:528:DyaL28Xos1OqtA%3D%3D Occurrence Handle3878084
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Albaugh, G., Bellavance, E., Strande, L. et al. Nicotine Induces Mononuclear Leukocyte Adhesion and Expression of Adhesion Molecules,VCAM and ICAM, in Endothelial Cells In Vitro. Ann Vasc Surg 18, 302–307 (2004). https://doi.org/10.1007/s10016-004-0030-9
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10016-004-0030-9