Preventive Role of Tetraspanin CD9 in Systemic Inflammation of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is frequently associated with extrapulmonary complications, including cardiovascular disease, diabetes, and osteoporosis. Persistent, low-grade, systemic inflammation underlies these comorbid disorders. Tetraspanins, which have a characteristic structure spanning the membrane four times, facilitate lateral organization of molecular complexes and thereby form tetraspanin-enriched microdomains that are distinct from lipid rafts. Recent basic research has suggested a preventive role of tetraspanin CD9 in COPD. CD9-enriched microdomains negatively regulate LPS-induced receptor formation by preventing CD14 from accumulating into the rafts, and decreased CD9 in macrophages enhances inflammation in mice. Mice doubly deficient in CD9 and a related tetraspanin, CD81, show pulmonary emphysema, weight loss, and osteopenia, a phenotype akin to human COPD. A therapeutic approach to up-regulating CD9 in macrophages might improve the clinical course of patients with COPD with comorbidities.