Jae Young Choi1,2
, Monal Khansaheb1,3
, Nam Soo Joo1
Mauri E. Krouse1
, Robert C. Robbins4
, David Weill5
and Jeffrey J. Wine1
1Cystic Fibrosis Research Laboratory, Stanford University, Stanford,
2Department of Otorhinolaryngology, Yonsei University,
Seoul, Republic of Korea.
3Department of Pediatrics, UCSF, San
Francisco, California, USA.
4Department of Cardiothoracic Surgery
5Department of Pulmonary and Critical Care Medicine, Stanford
University School of Medicine, Stanford, California, USA.
Address correspondence to: Jeffrey J. Wine, Cystic Fibrosis Research Laboratory,
Room 450, Bldg. 420, Main Quad, Stanford University, Stanford, California 94305-2130,
USA. Phone: (650) 725-2462; Fax: (650) 725-5699.
Published April 20, 2009
Received for publication August 27, 2008, and accepted in revised form February
Chronic bacterial airway infections are the major cause of mortality in cystic
fibrosis (CF). Normal airway defenses include reflex stimulation of submucosal
gland mucus secretion by sensory neurons that release substance P (SubP). CFTR
is an anion channel involved in fluid secretion and mutated in CF; the role of
CFTR in secretions stimulated by SubP is unknown. We used optical methods to
measure SubP-mediated secretion from human submucosal glands in lung transplant
tissue. Glands from control but not CF subjects responded to mucosal chili oil.
Similarly, serosal SubP stimulated secretion in more than 60% of control glands
but only 4% of CF glands. Secretion triggered by SubP was synergistic with
vasoactive intestinal peptide and/or forskolin but not with carbachol; synergy
was absent in CF glands. Pig glands demonstrated a nearly 10-fold greater
response to SubP. In 10 of 11 control glands isolated by fine dissection, SubP
caused cell volume loss, lumen expansion, and mucus flow, but in 3 of 4 CF
glands, it induced lumen narrowing. Thus, in CF, the reduced ability of mucosal
irritants to stimulate airway gland secretion via SubP may be another factor
that predisposes the airways to infections.