Immunogenetic programs for viral induction of mucous cell metaplasia

Michael J. Holtzman, John T. Battaile, Anand C. Patel

Research output: Contribution to journalReview articlepeer-review

5 Scopus citations

Abstract

Mucous secretions are frequently implicated in the morbidity and mortality associated with respiratory illness and airway disease, but we still do not understand precisely how these secretions develop or how to control them. A likely possibility is that the increased mucus is a consequence of overproduction and subsequent secretion in the setting of mucous cell metaplasia. In that regard, airway inflammatory diseases are invariably characterized by excessive mucous cell metaplasia, but precisely how inflammatory stimuli might influence mucous cell levels remains uncertain. We have used mouse models of viral bronchiolitis in concert with studies of patients with hypersecretory airway disease to define the cellular and molecular mechanisms for mucous cell metaplasia. Here we review our recent work that defines upstream immune events and downstream epithelial events that drive persistent mucous cell metaplasia. To date, we now recognize that upstream events include a new immune axis for growth factor and cytokine production and downstream events that include ciliated epithelial cell survival and transdifferentiation to mucous cells as well as expression of chloride channel calcium-activated (Clca) genes. To the extent that we can monitor these events in humans, it appears that similar alterations are found in patients with asthma and patients with chronic obstructive pulmonary disease (COPD). Together, the studies achieve more precise definition of just how viruses reprogram airway behavior and thereby provide a more rational basis for restoring epithelial architecture to normal.

Original languageEnglish (US)
Pages (from-to)29-39
Number of pages11
JournalAmerican journal of respiratory cell and molecular biology
Volume35
Issue number1
DOIs
StatePublished - Jul 2006

Keywords

  • Airway epithelial cell
  • Airway hyperreactivity
  • Apoptosis
  • Asthma
  • Chronic obstructive pulmonary disease
  • Mucosal immunity

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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