Cigarette smoke impairs clearance of apoptotic cells through oxidant-dependent activation of RhoA.

ABSTRACT:

Rationale

Cigarette smoke (CS) is the primary cause of chronic obstructive pulmonary disease (COPD), an effect that is, in part, due to intense oxidant stress. Clearance of apoptotic cells (efferocytosis) is a critical regulator of lung homeostasis, which is defective in smokers and in patients with COPD, suggesting a role in disease pathogenesis.

Objectives

We hypothesized that CS would impair efferocytosis through oxidant-dependent activation of RhoA, a known inhibitor of this process.

Methods

We investigated the effect of CS on efferocytosis in vivo and ex vivo, using acute, subacute, and long-term mouse exposure models.

Measurements and main results

Acute and subacute CS exposure suppressed efferocytosis by alveolar macrophages in a dose-dependent, reversib

SUBMITTER: Richens TR 

PROVIDER: S-EPMC2689911 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature