Airway epithelial injury is considered critical for the development of small airways
fibrosis present in posttransplant chronic lung allograft dysfunction (CLAD). Club
cells (formerly known as Clara cells) are nonciliated, secretory cells of the airway
epithelium, mainly situated in the terminal and respiratory bronchioles, identified
by expression of club cell secretory protein (CCSP) (also known as CC-16, CC-10, uteroglobin,
or secretoglobin family 1A member 1 [SCGB1A1]). In physiological conditions, club
cells, which constitute up to 44% of all proliferating cells in the small airways,
function as epithelial progenitors for regeneration and repair of lung injury.
1
,2
Moreover, club cells are thought to play a vital role in lung host defenses, by regulating
pulmonary homeostasis and modulating the pulmonary immune system via CCSP, which displays
broad anti-inflammatory, antioxidative, and immunoregulatory functions. For instance,
CCSP inhibits phospholipase A2, expressed by alveolar macrophages and airway epithelial cells, which is the primary
enzyme responsible for inflammatory arachidonic acid release.
3
CCSP also inhibits the release of oxidants from activated neutrophils and enhances
their phagocytic ability.
4
Club cells are the principal site of localization of the cytochrome P-450 monooxygenase
system in the human airway tract, and engage in xenobiotic metabolism of inhaled compounds,
such as chemicals (i.e., sulfur mustard, naphthalene, chlorine, and diacetyl), particulate
matter (i.e., cigarette smoke) and toxins.
5
,6
Club cell metabolism, injury, loss and/or alterations in CCSP levels have all been
associated with pathophysiologic small airways remodeling, and the presence of obliterative
or constrictive bronchiolitis, in inhalation exposures,
6
chronic obstructive pulmonary disease,
7
asthma,
8
and cystic fibrosis.
9
A key role for club cells has also been demonstrated in the onset of pulmonary fibrosis.
10
,11
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Article info
Publication history
Published online: February 09, 2023
Publication stage
In Press Journal Pre-ProofFootnotes
Editorial to: JHLT-D-22-00751 Early posttransplant reductions in club cell secretory protein associate with future risk for chronic allograft dysfunction in lung recipients: results from a multicenter study.
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