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Gastrin‐Releasing Peptide (GRP) Mediates Early Radiation‐Induced Airway Responses Predictive of Later Lung Injury
Author(s) -
Sunday Mary E,
Zhou Shutang,
Kant Erin Potts,
Jackson Isabel L,
Vujaskovic Zelcko,
Foster W. Michael
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb448
Subject(s) - gastrin releasing peptide , bronchoalveolar lavage , medicine , lung , fibrosis , pneumonitis , pulmonary fibrosis , airway , pulmonary function testing , immunology , pathology , endocrinology , receptor , bombesin , anesthesia , neuropeptide
Ionizing radiation (RT) induces lung injury, with pneumonitis 1–4 months later and fibrosis 4–6 months later, but early detection of RT lung injury is elusive. We recently showed GRP mediates RT‐induced pulmonary fibrosis in mice. GRP also mediates asthmatic responses in mice. We tested whether RT triggers airway responses via GRP. C57BL/6 (pneumonitis‐resistant) and C57L/J (pneumonitis‐sensitive) mice were exposed to thoracic RT (5,10, or 15Gy), followed by GRP blockade (small molecule 77427 or mAb 2A11) one‐hour later. We tested pulmonary function 6–72h post‐RT with bronchoalveolar lavage (BAL) for cells, cytokines, and albumin. RT‐dose‐dependent airway hyperreactivity (AHR) was increased 6–72h post‐RT, C57L/J>;C57BL/6, abrogated by GRP blockade. Only C57L/J responded to low‐dose RT. GRPR‐null mice had no AHR. C57L/J had elevated IL‐6 and γIFN in BAL, but C57BL/6 did not. GRP mRNA was highest in lungs of C57L/J. RT also increased vascular permeability via GRP, measured by BAL albumin levels 6–24h post‐RT, C57L/J>;C57BL/6. Thus, early pulmonary function testing could identify individuals most susceptible to developing fibrosis following radiation exposure.