Mucins MUC5AC and MUC5B Are Variably Packaged in the Same and in Separate Secretory Granules

Oanh N. Hoang, Anna Ermund, Ana M. Jaramillo, Dalia Fakih, Cory B. French, Jose R. Flores, Harry Karmouty-Quintana, Jesper M. Magnusson, Giorgio Fois, Michael Fauler, Manfred Frick, Peter Braubach, Joshua B. Hales, Richard C. Kurten, Reynold Panettieri, Leoncio Vergara, Camille Ehre, Roberto Adachi, Michael J. Tuvim, Gunnar C. HanssonBurton F. Dickey

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Rationale: MUC5AC (mucin 5AC, oligomeric gel-forming) and MUC5B (mucin 5B, oligomeric gel-forming) are the predominant secreted polymeric mucins in mammalian airways. They contribute differently to the pathogenesis of various muco-obstructive and interstitial lung diseases, and their genes are separately regulated, but whether they are packaged together or in separate secretory granules is not known. Objectives: To determine the packaging of MUC5AC and MUC5B within individual secretory granules in mouse and human airways under varying conditions of inflammation and along the proximal-distal axis. Methods: Lung tissue was obtained from mice stimulated to upregulate mucin production by the cytokines IL-1β and IL-13 or by porcine pancreatic elastase. Human lung tissue was obtained from donated normal lungs, biopsy samples of transplanted lungs, and explanted lungs from subjects with chronic obstructive pulmonary disease. MUC5AC and MUC5B were labeled with antibodies from different animal species or, in mice only, by transgenic chimeric mucin-fluorescent proteins and imaged using widefield deconvolution or Airyscan fluorescence microscopy. Measurements and Main Results: In both mouse and human airways, most secretory granules contained both mucins interdigitating within the granules. Smaller numbers of granules contained MUC5B alone, and even fewer contained MUC5AC alone. Conclusions: MUC5AC and MUC5B are variably stored both in the same and in separate secretory granules of both mice and humans. The high fraction of granules containing both mucins under a variety of conditions makes it unlikely that their secretion can be differentially controlled as a therapeutic strategy. This work also advances knowledge of the packaging of mucins within secretory granules to understand mechanisms of epithelial stress in the pathogenesis of chronic lung diseases.

Original languageEnglish (US)
Pages (from-to)1081-1095
Number of pages15
JournalAmerican journal of respiratory and critical care medicine
Issue number9
StatePublished - Nov 1 2022

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


  • airway mucins
  • club cells
  • MUC5AC
  • MUC5B
  • mucus


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