Effects of nicotine on intercellular adhesion molecule expression in endothelial cells and integrin expression in neutrophils in vitro.
OBJECTIVE
We previously reported that nicotine decreases leukocyte adhesion to uterine vascular endothelial cells in vivo under ischemic conditions in pregnant rabbits. To further investigate the mechanism of decreased leukocyte-endothelial adhesion by nicotine exposure, the effect of nicotine on endothelial cell intercellular adhesion molecule expression and neutrophil integrin expression of CD62L, CD11a, and CD11b were examined.


METHODS
Endothelial cells were isolated from human umbilical cord veins from normal pregnancies in nonsmoking women immediately after delivery. Neutrophils were isolated from healthy nonpregnant and nonsmoking female volunteers. First passage of endothelial cells and fresh isolated neutrophils were exposed to nicotine at different concentrations. Surface adhesion molecule expression of intercellular adhesion molecule on endothelial cells was determined by colorimetric assay. Neutrophil integrin expressions for CD62L, CD11a, and CD11b were determined by flow cytometry. Messenger RNA expression for intercellular adhesion molecule in endothelial cells was examined by reverse transcription-polymerase chain reaction.


RESULTS
Nicotine at a lower concentration of 0.01 micromol/L had no effect on endothelial cell surface intercellular adhesion molecule expression compared with controls (P =.614). Nicotine at a higher concentration of 10 micromol/L completely inhibited endothelial cell surface intercellular adhesion molecule-1 expression(P <.0001). At concentrations between 0.10 and 10 micromol/L, nicotine inhibited intercellular adhesion molecule expression in a dose-dependent manner. Messenger RNA expression of intercellular adhesion molecule in endothelial cells was not changed after exposure to nicotine. Decreased integrin expressions of CD62L, CD11a, and CD11b were observed on neutrophils after exposure to nicotine.


CONCLUSIONS
Nicotine exerts inhibitory effects on both endothelial cell surface intercellular adhesion molecule expression and neutrophil integrin expressions of CD62L, CD11a, and CD11b in vitro. These in vitro effects of nicotine may relate to the clinical observation of reduced incidence of preeclampsia in women that smoke.
Speer
Paul
P
Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport 71130, USA.
Zhang
Yanping
Y
Gu
Yang
Y
Lucas
Michael J
MJ
Wang
Yuping
Y
D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019041:L-Selectin / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism*; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D009994:Osmolar Concentration; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D014471:Umbilical Veins
D015815:Cell Adhesion Molecules; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D018722:Nicotinic Agonists; D012333:RNA, Messenger; D019041:L-Selectin; D009538:Nicotine