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Topical cathelicidin (LL‐37) an innate immune peptide induces acute olfactory epithelium inflammation in a mouse model
Author(s) -
Alt Jeremiah A.,
Qin Xuan,
Pulsipher Abigail,
Orb Quinn,
Orlandi Richard R.,
Zhang Jianxing,
Schults Austin,
Jia Wanjian,
Presson Angela P.,
Prestwich Glenn D.,
Oottamasathien Siam
Publication year - 2015
Publication title -
international forum of allergy and rhinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.503
H-Index - 46
eISSN - 2042-6984
pISSN - 2042-6976
DOI - 10.1002/alr.21634
Subject(s) - inflammation , medicine , infiltration (hvac) , pathology , mast cell , innate immune system , immune system , myeloperoxidase , cathelicidin , olfactory mucosa , immunology , tryptase , edema , olfactory system , physics , psychiatry , thermodynamics
Background Cathelicidin (LL‐37) is an endogenous innate immune peptide that is elevated in patients with chronic rhinosinusitis (CRS). The role of LL‐37 in olfactory epithelium (OE) inflammation remains unknown. We hypothesized that: (1) LL‐37 topically delivered would elicit profound OE inflammation; and (2) LL‐37 induced inflammation is associated with increased infiltration of neutrophils and mast cells. Methods To test our hypothesis we challenged C57BL/6 mice intranasally with increasing concentrations of LL‐37. At 24 hours tissues were examined histologically and scored for inflammatory cell infiltrate, edema, and secretory hyperplasia. In separate experiments, fluorescently conjugated LL‐37 was instilled and tissues were examined at 0.5 and 24 hours. To test our last hypothesis, we performed tissue myeloperoxidase (MPO) assays for neutrophil activity and immunohistochemistry for tryptase to determine the mean number of mast cells per mm 2 . Results LL‐37 caused increased inflammatory cell infiltrate, edema, and secretory cell hyperplasia of the sinonasal mucosa, with higher LL‐37 concentrations yielding significantly more inflammatory changes ( p < 0.01). Fluorescent LL‐37 demonstrated global sinonasal epithelial binding and tissue distribution. Further, higher concentrations of LL‐37 led to significantly greater MPO levels with dose‐dependent increases in mast cell infiltration ( p < 0.01). Conclusion LL‐37 has dramatic inflammatory effects in the OE mucosa that is dose‐dependent. The observed inflammatory changes in the olfactory mucosa were associated with the infiltration of both neutrophils and mast cells. Our biologic model represents a new model to further investigate the role of LL‐37 in OE inflammation.