Survey Anatomy of the Paranasal Sinuses in the Normal Mouse

Jacob, Abraham; Chole, Richard A.

doi:10.1097/01.mlg.0000202085.23454.2f

Cited by 35 publications

(31 citation statements)

References 12 publications

(13 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Mice do not have the same sinonasal anatomic structure as humans with 2/3rds of the sinonasal mucosa in mice dedicated to olfaction, although, mice have clearly discernible anterior and posterior ethmoid sinuses, sphenoid sinuses and a true maxillary and secondary maxillary sinus. 43 Innate immune response also differs between mice and humans. LL-37 induced inflammation in the mouse model may not accurately reflect the multifactorial pathophysiology of human CRS.…”

Section: Discussionmentioning

confidence: 99%

Topical cathelicidin (LL‐37) an innate immune peptide induces acute olfactory epithelium inflammation in a mouse model

Alt

Qin

Pulsipher

et al. 2015

Int Forum Allergy Rhinol

View full text Add to dashboard Cite

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 mm2. 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). Conclusions 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.

show abstract

Section: Discussionmentioning

confidence: 99%

Topical cathelicidin (LL‐37) an innate immune peptide induces acute olfactory epithelium inflammation in a mouse model

Alt

Qin

Pulsipher

et al. 2015

Int Forum Allergy Rhinol

View full text Add to dashboard Cite

show abstract

“…[62,63] It is plausible that LL-37-induced inflammation in the mouse may not accurately reflect the multifactorial physiology of the human condition. However, understanding the early underpinnings of the inflammatory response in the sinonasal cavity will enable us to design strategies to prevent these changes from occurring.…”

Section: Discussionmentioning

confidence: 99%

Prevention of sinonasal inflammation by a synthetic glycosaminoglycan

Pulsipher

Qin

Thomas

et al. 2016

Int Forum Allergy Rhinol

View full text Add to dashboard Cite

Background Glycosaminoglycans (GAGs) are polysaccharides that are distributed on respiratory epithelial cells, endothelial cells, and submucosal glands. Uniquely positioned, certain GAGs exhibit anti-inflammatory properties in respiratory diseases and serve important roles in repairing mucosal surfaces and modulating mucociliary clearance. We hypothesized that topical administration of a synthetic GAG (GM-0111) would prevent sinonasal inflammation in a mouse model of rhinosinusitis (RS). Methods To test our hypothesis, C57BL/6 mice were intranasally administered fluorescent GM-0111, and sinonasal tissues were examined for coating and penetration ability. To test therapeutic feasibility, mice (n = 6) were given GM-0111 or hyaluronic acid (HA) (800 μg dose) prior to inducing RS with inflammatory molecule LL-37 (115 μg dose). After 24 h, sinonasal tissues were harvested for histological and biochemical analysis of inflammatory markers (inflammatory cell infiltration, lamina propria (LP) thickening, and neutrophil enzyme myeloperoxidase (MPO)) and cell death. Results (1) GM-0111 was observed within sinonasal tissues 1 h and 24 h after intranasal administration, indicating rapid and effective coating and penetration. (2) GM-0111 prevented sinonasal tissues from developing inflammatory changes, with significant reductions in mast cell infiltration (p < 0.05), LP thickening (p < 0.001), and MPO levels (p < 0.01) when compared to tissues treated with LL-37 and those pre-treated with HA. (3) GM-0111 reduced cell death within sinonasal tissues in contrast to LL-37-treated tissues. Conclusions We report a new synthetic GAG (GM-0111) that uniformly coats and penetrates into the sinonasal mucosa to prevent sinonasal inflammation and cell death in a mouse model of RS.

show abstract

“…However most of these studies have been based on inappropriate application of mouse anatomy to human disease. Specifically, the airspaces between the ethmoid turbinates of mice ( Figure 3B), have been misinterpreted to be analogous to human ethmoid sinuses (Bomer et al 1998;Jacob and Chole 2006;Lindsay et al 2006;Phillips et al 2009). Ethmoid turbinates in mice do not enclose sinus airways, are lined predominantly by olfactory neuroepithelium, and receive significant airflow Kimbell et al 1997).…”

Section: Paranasal Airwaysmentioning

confidence: 99%