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  • Depletion of bone marrow CCSP-expressing cells delays airway regeneration.

Depletion of bone marrow CCSP-expressing cells delays airway regeneration.

Molecular therapy : the journal of the American Society of Gene Therapy (2014-11-21)
Martha L Bustos, Marco Mura, David Hwang, Olga Ludkovski, Amy P Wong, Armand Keating, Thomas K Waddell
ABSTRACT

The contribution of bone marrow cells (BMC) in lung repair is controversial. We previously reported a subpopulation of BMC that express Clara cell secretory protein (CCSP). To determine the contribution of endogenous CCSP(+) BMC to airway regeneration, we performed bone marrow transplantation studies using the CCtk mouse, which expresses a thymidine kinase suicide gene under regulation of the CCSP promoter. Mice were transplanted with wild-type or CCtk BMC and treated with ganciclovir to eliminate CCSP(+) cells. After airway injury using naphthalene, mice depleted of CCSP(+) BMC had more inflammatory cells in lung and decreased levels of oxygen in arterial blood. They also had reduced expression of airway epithelial genes and less Clara cells compared to control mice that had intact CCSP(+) BMC and bone marrow derived CCSP(+) cells in the airways. After naphthalene injury, administration of CCSP reproduced the beneficial effect of CCSP(+) BMC by improving recovery of airway epithelium, reducing lung inflammation and increasing oxygen in arterial blood from mice depleted of CCSP(+) BMC. Our data demonstrate that ablation of CCSP(+) BMC delays airway recovery and suggests the beneficial effect of CCSP(+) BMC in lung recovery is in part due to production of CCSP itself.

MATERIALS
Product Number
Brand
Product Description

Supelco
Melting point standard 79-81°C, analytical standard
Sigma-Aldrich
DAPI, for nucleic acid staining
Supelco
Naphthalene, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
Sigma-Aldrich
Naphthalene, 99%
Supelco
Naphthalene, analytical standard
Sigma-Aldrich
Naphthalene, suitable for scintillation, ≥99%
Sigma-Aldrich
4-Bromomethyl-7-methoxycoumarin, 97%
Supelco
Naphthalene, Pharmaceutical Secondary Standard; Certified Reference Material