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A new RAGE blocker, low anti‐coagulant 2‐O,3‐O desulfated heparin (ODSH), diminishes smoke‐induced pulmonary inflammation
Author(s) -
Sefcik Tayler L,
Fredrickson Ali C,
Reynolds Paul R
Publication year - 2011
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.25.1_supplement.114.5
Subject(s) - bronchoalveolar lavage , rage (emotion) , inflammation , pharmacology , receptor , medicine , glycation , smoke , immunology , cytokine , chemistry , lung , biology , neuroscience , organic chemistry
Research performed in our lab has implicated the receptor for advanced glycation end‐products (RAGE), a pattern recognition receptor, in pulmonary inflammation induced by tobacco smoke, diesel particulate matter, and hyperoxia. Recent work has also demonstrated that low anti‐coagulant 2‐O,3‐O‐desulfated heparin (ODSH) may function as an effective blocker of RAGE‐ligand interactions as evidenced by inhibition of RAGE ligation with its disparate ligands including CML‐BSA (AGE), HMGB‐1, and S100b. The current study sought to characterize the anti‐inflammatory effects of ODSH in BALB/c mice exposed to acute tobacco smoke. Mice were anesthetized and administered PBS or cigarette smoke extract (CSE, 0.02 cigarettes per dose) +/− 50 ug ODSH via nasal installation. Bronchoalveolar lavage fluid (BALF) was obtained 48 hours after exposure and analyzed. CSE induced a significant increase in total protein, total leukocyte count, PMN count, and cytokine concentration including TNF‐alpha in BALF. ODSH administration resulted in a significant decrease in CSE‐induced total protein, PMN quantity, and cytokine concentration in BALF compared to controls. The data show that ODSH blockade of RAGE and parallel signaling mechanisms can diminish smoke‐induced pro‐inflammatory events. Work was supported by the Flight Attendant¡¦s Medical Research Institute (FAMRI, PRR) and a BYU Mentoring Environment Grant (PRR).