Adhesion Molecules and Smoking - Adhesion Molecules - page 259

CHRONIC AIRWAY DISEASE
Chronic Inflammation
Chronic airway inl ammation is an important component of pulmonary diseases
such as COPD and asthma. Cigarette smoking increases the risk of, and worsens
the course of, these diseases. h e enhancement of cellular adhesion molecules is
one part of a molecular cascade facilitating inl ammatory damage to lung tissue.
ICAM-1 is an important mediator for the recruitment, retention, and activation of
neutrophils in chronic airway inl ammation. Environmental stimuli can activate
alveolar macrophages, inducing the expression of IL-1β, TNF-α, and other pro-
inl ammatory cytokines. Consequently, this stimulates ICAM-1 expression,
enhancing leukocyte ini ltration and inl ammatory injury (Churchill et al. 1993).
h e inl ammation induced by smoke exposure is reversible in the early stages.
However, once chronic inl ammation has been established, persistent pathological
change occurs in the airway. Using a rat model, chronic bronchitis and pathological
changes were induced within 7 wk of smoke exposure (Li et al. 2007). h ese
inducible pathological changes were associated with increased inl ammation. An
increase in neutrophils in bronchoalveolar lavage l uid (BALF) is noted as early
as 2 wk at er onset of smoke exposure. Additionally, increased expression of
ICAM-1 was found in the airway tissue. h e pathological changes, inl ammation,
and elevations in ICAM-1 were all reversible, to some degree, with cessation of
smoking. h is reversal of pathological changes is a function of time; the longer the
smoking exposure, the less likely the pathologic changes are to resolve.
Cessation of smoking does not lead to complete reversal of systemic
inl ammation. One interpretation of this i nding is that systemic inl ammation
from sources other than smoking predisposes individuals to develop chronic
inl ammatory conditions such as COPD (Gan et al. 2004). Smoking then exacerbates
this systemic inl ammation by altering ICAM-1 expression. h is is supported by
the observation that COPD ot en is accompanied by other inl ammatory diseases,
such as CVD and osteoporosis. Systemic inl ammation is associated with both
asthma and COPD, and increased concentrations of sICAM-1 are found in patients
who develop severe pulmonary disease (Hollander et al. 2007). Serum sE-selectin,
another biomarker for inl ammation, is also elevated in individuals with COPD
and chronic bronchitis (Riise et al. 1994).
Pathological Changes in the Human Airway
In humans, increased ICAM-1 expression is found in the pulmonary vasculature
of current smokers (Schaberg et al. 1996). Individuals underwent lung biopsy
in evaluation of a peripheral lung tumor. Dif erences in VCAM-1, E-selectin,
and P-selectin were not observed between smokers and non-smokers. ICAM-1
expression increased linearly by pack-year history of smoking, thus showing