Adhesion Molecules and Smoking - Adhesion Molecules - page 260

a duration-response to cigarette smoke exposure. h ese i ndings may not be
generalizable, as 24 of 26 patients in this study had a bronchial cancer. h e authors
cite the inability to recruit healthy volunteers for lung biopsy as justii cation for
studying individuals requiring lung biopsy for evaluation of a pulmonary mass.
h e tumors in this group, however, were not squamous cell carcinomas, not
thought to be associated with smoking, and unlikely to alter the interpretation of
their i ndings.
In children with asthma, BALF concentrations of sICAM-1 were higher among
those with active disease than those with recent asthma l ares. sICAM-1 does not
correlate with either neutrophil or eosinophil counts in children with asthma. Also,
sICAM-1 in BALF correlated with i ndings on chest x-ray suggestive of dif use
airway inl ammation (Marguet et al. 2000). sICAM-1 concentrations are elevated
among patients experiencing acute asthma exacerbations in comparison to control
patients as well as those with stable disease. Consistent with the association of
sICAM-1 with airway inl ammation, the production of sICAM-1 is inhibited
by corticosteroid administration (Ren-Bin Tang et al. 2002). Concentrations of
sVCAM-1 and sE-selectin also are elevated among patients with acute asthma
l ares (Riise et al. 1994, Ren-Bin Tang et al. 2002). If the airway inl ammation of
asthma is mediated via cellular adhesion molecules, tobacco smoke may worsen
the course via upregulation of expression of these molecules.
BASIC SCIENCE
Altered Leukocyte/Endothelium Interaction
Since the epidemiological association of smoking and disease, insight to the
molecular pathways involved has been garnered. h e study of these pathways is
dii cult, as smoke from a burning cigarette is a complex mixture of both gaseous
and particulate matter from approximately 4,000 dif erent components (Table 3) .
h e constituent molecules may act singly or in combination to cause disease.
Particulate cigarette smoke condensate (CSC) can be collected and used for
research purposes. h e expression of ICAM-1, ELAM-1, and VCAM-1 on human
and bovine endothelial cells is increased when cell cultures are exposed to CSC
(Kalra et al. 1994).
CSC af ects both leukocyte adhesion and leukocyte transmigration. Time- and
dose-dependent increases in adhesion molecule expression and monocyte adhesion
to endothelial cells is demonstrated with exposure of endothelial cells to CSC at
concentrations lower than those obtained from a single cigarette. h e monocyte-
endothelial cell interaction can be blocked with antibodies against CD11b (an
adhesive ligand; ICAM-1 functions as a CD11b receptor), with protein kinase
C (PKC) inhibitors, and with anti-inl ammatory medications (Kalra et al. 1994,
Shen et al. 1996). Activation of PKC leads to increased binding activity of nuclear