BACKGROUND: Lower respiratory tract infection is a differentiating feature of children with poorly controlled asthma. OBJECTIVE: Given the role of alveolar macrophages (AMs) in innate immunity, we hypothesized that AM phagocytosis might be impaired in poorly controlled asthma. METHODS: Bronchoalveolar lavage fluid AMs were isolated from 28 asthmatic children (moderate asthma, n = 12; severe asthma, n = 16), 10 nonasthmatic children with chronic cough treated with inhaled corticosteroids, and 10 healthy adult control subjects. AMs were stimulated with LPS and exposed to fluorescein isothiocyanate-conjugated Staphylococcus aureus for 2 hours. Phagocytosis was quantified by using a phagocytic index (PI) calculated from the percentage of phagocytic cells multiplied by the relative fluorescence (RFU) units of S. aureus per cell. Apoptosis was determined from the percentage of cells positive for poly (adenosine diphosphate-ribose) polymerase. RESULTS: Phagocytosis as measured by using the unstimulated PI was decreased in subjects with poorly controlled asthma (healthy control subjects, 9330 +/- 3992 RFU; chronic cough, 9042 +/- 5976 RFU; moderate asthma, 4361 +/- 2536 RFU; severe asthma, 3153 +/- 1886 RFU; P < .001) and remained unchanged with LPS stimulation. Children with severe asthma also had increased AM apoptosis, both the unstimulated and LPS-simulated states (P < .001), which correlated with the PI. CONCLUSIONS: AM function is compromised in children with poorly controlled asthma and is characterized by decreased phagocytosis and increased apoptosis.
BACKGROUND: Lower respiratory tract infection is a differentiating feature of children with poorly controlled asthma. OBJECTIVE: Given the role of alveolar macrophages (AMs) in innate immunity, we hypothesized that AM phagocytosis might be impaired in poorly controlled asthma. METHODS: Bronchoalveolar lavage fluid AMs were isolated from 28 asthmatic children (moderate asthma, n = 12; severe asthma, n = 16), 10 nonasthmatic children with chronic cough treated with inhaled corticosteroids, and 10 healthy adult control subjects. AMs were stimulated with LPS and exposed to fluorescein isothiocyanate-conjugated Staphylococcus aureus for 2 hours. Phagocytosis was quantified by using a phagocytic index (PI) calculated from the percentage of phagocytic cells multiplied by the relative fluorescence (RFU) units of S. aureus per cell. Apoptosis was determined from the percentage of cells positive for poly (adenosine diphosphate-ribose) polymerase. RESULTS: Phagocytosis as measured by using the unstimulated PI was decreased in subjects with poorly controlled asthma (healthy control subjects, 9330 +/- 3992 RFU; chronic cough, 9042 +/- 5976 RFU; moderate asthma, 4361 +/- 2536 RFU; severe asthma, 3153 +/- 1886 RFU; P < .001) and remained unchanged with LPS stimulation. Children with severe asthma also had increased AM apoptosis, both the unstimulated and LPS-simulated states (P < .001), which correlated with the PI. CONCLUSIONS: AM function is compromised in children with poorly controlled asthma and is characterized by decreased phagocytosis and increased apoptosis.
Authors: Borja G Cosío; Buphinder Mann; Kazuhiro Ito; Elen Jazrawi; Peter J Barnes; K Fan Chung; Ian M Adcock Journal: Am J Respir Crit Care Med Date: 2004-04-15 Impact factor: 21.405
Authors: Xuejun J Yin; Caroline C Dong; Jane Y C Ma; James M Antonini; Jenny R Roberts; Charles F Stanley; Rosana Schafer; Joseph K H Ma Journal: Toxicol Sci Date: 2003-12-02 Impact factor: 4.849
Authors: Peter W Heymann; Holliday T Carper; Deborah D Murphy; Thomas A E Platts-Mills; James Patrie; Anne P McLaughlin; Elizabeth A Erwin; Marcus S Shaker; Martha Hellems; Jehanna Peerzada; Frederick G Hayden; Tina K Hatley; Rachel Chamberlain Journal: J Allergy Clin Immunol Date: 2004-08 Impact factor: 10.793
Authors: Amy S Feldman; Yuan He; Martin L Moore; Marc B Hershenson; Tina V Hartert Journal: Am J Respir Crit Care Med Date: 2015-01-01 Impact factor: 21.405
Authors: Yong Gyu Lee; Jong Jin Jeong; Sharmilee Nyenhuis; Evgeny Berdyshev; Sangwoon Chung; Ravi Ranjan; Manjula Karpurapu; Jing Deng; Feng Qian; Elizabeth A B Kelly; Nizar N Jarjour; Steven J Ackerman; Viswanathan Natarajan; John W Christman; Gye Young Park Journal: Am J Respir Cell Mol Biol Date: 2015-06 Impact factor: 6.914
Authors: Anne M Fitzpatrick; Susan T Stephenson; Graham R Hadley; Leandrea Burwell; Madhuri Penugonda; Dawn M Simon; Jason Hansen; Dean P Jones; Lou Ann S Brown Journal: J Allergy Clin Immunol Date: 2011-04-22 Impact factor: 10.793
Authors: Anne M Fitzpatrick; W Gerald Teague; Leandrea Burwell; Meredith S Brown; Lou Ann S Brown Journal: Pediatr Res Date: 2011-02 Impact factor: 3.756
Authors: Mark T Kearns; Samay Dalal; Sarah A Horstmann; Tiffany R Richens; Takeshi Tanaka; Jenna M Doe; Darren M Boe; Norbert F Voelkel; Laimute Taraseviciene-Stewart; William J Janssen; Chun G Lee; Jack A Elias; Donna Bratton; Rubin M Tuder; Peter M Henson; R William Vandivier Journal: Am J Physiol Lung Cell Mol Physiol Date: 2012-02-03 Impact factor: 5.464
Authors: Loren C Denlinger; Ron L Sorkness; Wai-Ming Lee; Michael D Evans; Michele J Wolff; Sameer K Mathur; Gina M Crisafi; Katie L Gaworski; Tressa E Pappas; Rose F Vrtis; Elizabeth A Kelly; James E Gern; Nizar N Jarjour Journal: Am J Respir Crit Care Med Date: 2011-11-01 Impact factor: 21.405
Authors: Jenny E Han; Jessica A Alvarez; Jennifer L Jones; Vin Tangpricha; Mona A Brown; Li Hao; Lou Ann S Brown; Greg S Martin; Thomas R Ziegler Journal: Nutrition Date: 2017-02-27 Impact factor: 4.008