Monica G Lawrence1, W Gerald Teague2, Xin Feng3, Caitlin Welch4, Elaine Etter4, Julie Negri4, Marthajoy Spano5, Kristin Wavell2, Thomas Braciale6, John W Steinke7, Larry Borish8. 1. Department of Medicine, University of Virginia, Charlottesville, Virginia; Child Health Research Center, Department of Pediatrics, University of Virginia, Charlottesville, Virginia. Electronic address: ml4nz@virginia.edu. 2. Child Health Research Center, Department of Pediatrics, University of Virginia, Charlottesville, Virginia. 3. Department of Otorhinolaryngology, Qilu Hospital of Shandong University, Shandong, People's Republic of China; NHC Key Laboratory of Otorhinolaryngology, Shandong University, Jinan, Shandong, People's Republic of China. 4. Department of Medicine, University of Virginia, Charlottesville, Virginia. 5. Department of Pathology, University of Virginia, Charlottesville, Virginia. 6. Department of Pathology, University of Virginia, Charlottesville, Virginia; Department of Microbiology, University of Virginia, Charlottesville, Virginia. 7. Department of Medicine, University of Virginia, Charlottesville, Virginia; Genentech, Charlottesville, Virginia. 8. Department of Medicine, University of Virginia, Charlottesville, Virginia; Department of Microbiology, University of Virginia, Charlottesville, Virginia.
Abstract
BACKGROUND: Our previous studies revealed the presence of interleukin-5 (IL-5) receptor alpha chain (IL-5Rα, CD125) on neutrophils in a murine model of influenza and in the lung fluid of children with severe asthma. OBJECTIVE: To further evaluate the functional characteristics and effects of clinical factors and inflammatory variables on neutrophil surface IL-5Rα abundance in lung fluid and blood. METHODS: IL-5Rα expression was quantified by flow cytometry performed on purified neutrophils from blood and bronchoalveolar lavage fluid samples obtained from healthy controls and individuals with asthma. Expression was further confirmed by immunohistochemistry. Functional signaling through the IL-5Rα was evaluated by measurement of IL-5-inducible modulation of neutrophil surface CD62L and IL-5Rα expression. RESULTS: IL-5Rα was consistently present but at a variable magnitude on blood and lung neutrophils. Expression on lung neutrophils was significantly higher than that on blood cells (p"?>P < .001) where their expression was higher in the presence of airway pathogens, especially with respiratory viruses. Increased receptor expression occurred in response to the translocation of preformed receptors from intracellular stores. Receptors were functional as revealed by IL-5-mediated down-regulation of CD62L and the feed-forward up-regulation of reception expression. CONCLUSION: In addition to the expression on eosinophils and basophils, the IL-5Rα is consistently and abundantly expressed on the surface of blood and especially air space neutrophils. These observations support the concept that some of the efficacy of IL-5/IL-5R-targeting biologics observed in asthma may reflect their ability to target neutrophilic air space inflammation.
BACKGROUND: Our previous studies revealed the presence of interleukin-5 (IL-5) receptor alpha chain (IL-5Rα, CD125) on neutrophils in a murine model of influenza and in the lung fluid of children with severe asthma. OBJECTIVE: To further evaluate the functional characteristics and effects of clinical factors and inflammatory variables on neutrophil surface IL-5Rα abundance in lung fluid and blood. METHODS: IL-5Rα expression was quantified by flow cytometry performed on purified neutrophils from blood and bronchoalveolar lavage fluid samples obtained from healthy controls and individuals with asthma. Expression was further confirmed by immunohistochemistry. Functional signaling through the IL-5Rα was evaluated by measurement of IL-5-inducible modulation of neutrophil surface CD62L and IL-5Rα expression. RESULTS: IL-5Rα was consistently present but at a variable magnitude on blood and lung neutrophils. Expression on lung neutrophils was significantly higher than that on blood cells (p"?>P < .001) where their expression was higher in the presence of airway pathogens, especially with respiratory viruses. Increased receptor expression occurred in response to the translocation of preformed receptors from intracellular stores. Receptors were functional as revealed by IL-5-mediated down-regulation of CD62L and the feed-forward up-regulation of reception expression. CONCLUSION: In addition to the expression on eosinophils and basophils, the IL-5Rα is consistently and abundantly expressed on the surface of blood and especially air space neutrophils. These observations support the concept that some of the efficacy of IL-5/IL-5R-targeting biologics observed in asthma may reflect their ability to target neutrophilic air space inflammation.
Authors: Pia J Hauk; Marzena Krawiec; James Murphy; Juri Boguniewicz; Allison Schiltz; Elena Goleva; Andrew H Liu; Donald Y M Leung Journal: Pediatr Pulmonol Date: 2008-09
Authors: John W Steinke; Monica G Lawrence; W Gerald Teague; Thomas J Braciale; James T Patrie; Larry Borish Journal: J Allergy Clin Immunol Date: 2020-06-09 Impact factor: 14.290
Authors: Stacey A Gorski; Monica G Lawrence; Amy Hinkelman; MarthaJoy M Spano; John W Steinke; Larry Borish; W Gerald Teague; Thomas J Braciale Journal: PLoS One Date: 2019-08-15 Impact factor: 3.240