Defective phagocytosis in airways disease

Chest. 2012 Apr;141(4):1055-1062. doi: 10.1378/chest.11-2348.


Maintaining an airway clear of inhaled particles, pathogens, and cellular debris is paramount for lung homeostasis. In healthy individuals, the phagocytes of the innate immune system act as sentinels to patrol the airway and ensure sterility. However, in airways diseases, including asthma, COPD, and cystic fibrosis, there is a propensity for bacterial colonization that may contribute to disease worsening. Evidence suggests that this may be due to dysfunctional phagocytosis. In patients with COPD, phagocytosis of several bacterial species and removal of apoptotic cells (efferocytosis) by alveolar macrophages are significantly reduced; however, these cells can remove inert beads normally. Attenuated phagocytosis is also apparent in monocyte-derived macrophages from the same patients, suggesting an inherent defect in these cells. Reduced expression of cell surface recognition receptors has been suggested as one mechanism for these observations; however, the literature is currently contradictory and requires further clarification. In cystic fibrosis, a similar defect is also observed in both airway neutrophils and macrophages, leading to ineffective bacterial uptake and subsequent killing. In asthma and other airways diseases, there are also reports of defective phagocytosis of bacterial pathogens, although the relevance to disease pathophysiology is not understood. Oxidative stress is emerging as a common mechanism that may be altering both macrophage and neutrophil functions that can be reversed by various antioxidant strategies. The identification of this and other mechanisms underlying phagocyte dysfunction may present novel therapeutic opportunities for the treatment of many of these intractable diseases and improve patient morbidity and mortality.

Publication types

  • Review

MeSH terms

  • Asthma / microbiology
  • Asthma / physiopathology
  • Cystic Fibrosis / microbiology
  • Cystic Fibrosis / physiopathology
  • Humans
  • Phagocytosis / physiology*
  • Pulmonary Disease, Chronic Obstructive / microbiology
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Respiratory Tract Diseases / drug therapy
  • Respiratory Tract Diseases / microbiology
  • Respiratory Tract Diseases / physiopathology*