title: Cigarette smoking is associated with increased human monocyte adhesion to endothelial cells: reversibility with oral L-arginine but not vitamin C.
abstract: OBJECTIVE
  This study sought to assess the effect of cigarette smoking on adhesion of human monocytes to human endothelial cells and to measure the effect of L-arginine and vitamin C supplementation on this interaction.
  
  
  BACKGROUND
  Cigarette smoking has been associated with abnormal endothelial function and increased leukocyte adhesion to endothelium, both key early events in atherogenesis. Supplementation with both oral L-arginine (the physiologic substrate for nitric oxide) and vitamin C (an aqueous phase antioxidant) may improve endothelial function; however, their benefit in cigarette smokers is not known.
  
  
  METHODS
  Serum was collected from eight smokers (mean [+/-SD] age 33 +/- 5 years) with no other coronary risk factors and eight age- and gender-matched lifelong nonsmokers. The serum was added to confluent monolayers of human umbilical vein endothelial cells and incubated for 24 h. Human monocytes obtained by counterflow centrifugation elutriation were then added to these monolayers for 1 h, and adhesion then was measured by light microscopy. To assess reversibility, monocyte/ endothelial cell adhesion was then measured for each subject 2 h after 2 g of oral vitamin C and 2 h after 7 g of oral L-arginine.
  
  
  RESULTS
  In smokers compared with control subjects, monocyte/ endothelial cell adhesion was increased (46.4 +/- 4.5% vs. 27.0 +/- 5.2%, p < 0.001), endothelial expression of intercellular adhesion molecule (ICAM)-1 was increased (0.31 +/- 0.02 vs. 0.22 +/- 0.03, p = 0.004), and vitamin C levels were reduced (33.7 +/- 24.1 vs. 53.4 +/- 11.5 mumol/liter, p = 0.028). After oral L-arginine, monocyte/ endothelial cell adhesion was reduced in smokers (from 46.4 +/- 4.5% to 35.1 +/- 4.0%, p = 0.002), as was endothelial cell expression of ICAM-1 (from 0.31 +/- 0.02 to 0.27 +/- 0.01, p = 0.001). After vitamin C, there was no significant change in monocyte/ endothelial cell adhesion or ICAM-1 expression from baseline in the smokers despite an increase in vitamin C levels (to 115 +/- 7 mumol/liter).
  
  
  CONCLUSIONS
  Cigarette smoking is associated with increased monocyte-endothelial cell adhesion when endothelial cells are exposed to serum from healthy young adults. This abnormality is acutely reversible by oral L-arginine but not by vitamin C.
authors.affiliation: Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia.
authors.forename: M R
authors.initials: MR
authors.lastname: Adams
authors.forename: W
authors.initials: W
authors.lastname: Jessup
authors.forename: D S
authors.initials: DS
authors.lastname: Celermajer
mesh_terms: D000328:Adult; D001120:Arginine / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000502:physiology*; D012907:Smoking / Q000503:physiopathology*
chemical_list: D018799:Intercellular Adhesion Molecule-1; D001120:Arginine; D001205:Ascorbic Acid