Intercellular adhesion molecule 1 and progression of percent emphysema: The MESA Lung Study

Abstract

Endothelial intercellular adhesion molecule (ICAM) 1 binds neutrophils and facilitates their transmigration into the lung; E-selectin facilitates leukocyte rolling. As neutrophils contribute to tissue destruction in emphysema and chronic obstructive pulmonary disease, we hypothesized that soluble ICAM-1 (sICAM-1) and E-selectin (sE-selectin) would be associated with longitudinal progression of emphysema and lung function decline. The Multi-Ethnic Study of Atherosclerosis (MESA) enrolled participants 45-84 years old without clinical cardiovascular disease in 2000-02. The MESA Lung Study assessed percent emphysema (<-950 Hounsfield units) on cardiac (2000-07) and full-lung CT scans (2010-12), and spirometry was assessed twice over five years. sICAM-1 and sE-selectin were measured at baseline. Mixed-effect models adjusted for demographics, anthropometry, smoking, C-reactive protein, sphingomyelin and scanner factors. Among 1,865 MESA Lung participants with measurement of sICAM-1 and percent emphysema the mean log-sICAM-1 was 5.5±0.3 ng/mL and percent emphysema increased 0.73 percentage points (95% CI: 0.34, 1.12; P<0.001) over ten years. A one SD increase in sICAM-1 was associated with an accelerated increase in percent emphysema of 0.23 percentage points over ten years (95% CI: 0.06, 0.39; P=0.007). No significant association was found for sE-selectin, or between any adhesion molecule and lung function. Higher levels of sICAM-1 were independently associated with progression of percent emphysema in a general population sample.

The role of the endothelium in asthma and chronic obstructive pulmonary disease (COPD)

“…MAC-1 binds to intracellular adhesion molecule-1 (ICAM-1) on the surface of endothelial cells. Serum levels of ICAM-1 are inversely related to lung function and are also associated with increased percentages of emphysema on CT scan suggesting that this mechanism may be clinically relevant [18, 19]. Blocking the action of ICAM-1 in rodent models has also reduced pulmonary inflammation further supporting the possibility that the increase in ICAM-1 might be related to the increase in inflammation seen in COPD [20].…”

Biomarkers of Key Biological Pathways in CVD

“…Higher levels of sICAM-1 were associated with accelerated progression of emphysema in MESA, indicating that neutrophil recruitment to the lung, mediated by ICAM-1, may play a role in the progression of subclinical emphysema[12]. Similarly, higher levels of P-selectin were associated with peripheral arterial disease, suggesting that leukocytes recruitment to sites of vascular injury, mediated by P-selectin, may contribute to progression of peripheral arterial disease.…”

Emphysema Distribution and Diffusion Capacity Predict Emphysema Progression in Human Immunodeficiency Virus Infection

“…To provide context, other assessments of emphysema progression in non-HIV cohorts which have used a quantitative rather than qualitative approach through lung densitometry measurements have found that lower BMI[28], current smoking status[29], and female sex[29] are associated with more rapid emphysema progression. Circulating biomarkers such as soluble intercellular adhesion molecule (ICAM-1)[30], surfactant protein D[29] and soluble receptor for advanced glycation end product (sRAGE)[29] have also been shown to be higher in more rapid emphysema progressors.…”