RATIONALE: Eosinophil β1-integrin activation correlates inversely with FEV1 and directly with eosinophil-bound P-selectin in subjects with nonsevere allergic asthma. OBJECTIVES: Determine the relationships between β1-integrin activation and pulmonary function or eosinophil-bound P-selectin in subjects with asthma of varying severity and discern the source of eosinophil-bound P-selectin. METHODS: Blood was assayed by flow cytometry for P-selectin and activated β1-integrin on eosinophils and platelets. Plasma was analyzed with ELISA for soluble P-selectin, platelet factor 4, and thrombospondin-1. MEASUREMENTS AND MAIN RESULTS: Activated β1-integrin correlated with eosinophil-bound P-selectin among all subjects with asthma even though activated β1-integrin was higher in subjects with nonsevere asthma than severe asthma. Activated β1-integrin correlated inversely with FEV1 corrected for FVC only in younger subjects with nonsevere asthma. Paradoxically, platelet surface P-selectin, a platelet activation marker, was low in subjects with severe asthma, whereas plasma platelet factor 4, a second platelet activation marker, was high. Correlations indicated that P-selectin-positive platelets complexed to eosinophils are the major source of the eosinophil-bound P-selectin associated with β1-integrin activation. After whole-lung antigen challenge of subjects with nonsevere asthma, a model of asthma exacerbation known to cause platelet activation, circulating eosinophils bearing P-selectin and activated β1-integrin disappeared. CONCLUSIONS: The relationship between eosinophil β1-integrin activation and pulmonary function was replicated only for younger subjects with nonsevere asthma. However, we infer that platelet activation and binding of activated platelets to eosinophils followed by P-selectin-mediated eosinophil β1-integrin activation occur in both nonsevere and severe asthma with rapid movement of platelet-eosinophil complexes into the lung in more severe disease.
RATIONALE: Eosinophil β1-integrin activation correlates inversely with FEV1 and directly with eosinophil-bound P-selectin in subjects with nonsevere allergic asthma. OBJECTIVES: Determine the relationships between β1-integrin activation and pulmonary function or eosinophil-bound P-selectin in subjects with asthma of varying severity and discern the source of eosinophil-bound P-selectin. METHODS: Blood was assayed by flow cytometry for P-selectin and activated β1-integrin on eosinophils and platelets. Plasma was analyzed with ELISA for soluble P-selectin, platelet factor 4, and thrombospondin-1. MEASUREMENTS AND MAIN RESULTS: Activated β1-integrin correlated with eosinophil-bound P-selectin among all subjects with asthma even though activated β1-integrin was higher in subjects with nonsevere asthma than severe asthma. Activated β1-integrin correlated inversely with FEV1 corrected for FVC only in younger subjects with nonsevere asthma. Paradoxically, platelet surface P-selectin, a platelet activation marker, was low in subjects with severe asthma, whereas plasma platelet factor 4, a second platelet activation marker, was high. Correlations indicated that P-selectin-positive platelets complexed to eosinophils are the major source of the eosinophil-bound P-selectin associated with β1-integrin activation. After whole-lung antigen challenge of subjects with nonsevere asthma, a model of asthma exacerbation known to cause platelet activation, circulating eosinophils bearing P-selectin and activated β1-integrin disappeared. CONCLUSIONS: The relationship between eosinophil β1-integrin activation and pulmonary function was replicated only for younger subjects with nonsevere asthma. However, we infer that platelet activation and binding of activated platelets to eosinophils followed by P-selectin-mediated eosinophil β1-integrin activation occur in both nonsevere and severe asthma with rapid movement of platelet-eosinophil complexes into the lung in more severe disease.
Authors: David Ramos-Barbón; Rebeca Fraga-Iriso; Nadia S Brienza; Carmen Montero-Martínez; Héctor Verea-Hernando; Ron Olivenstein; Catherine Lemiere; Pierre Ernst; Qutayba A Hamid; James G Martin Journal: Am J Respir Crit Care Med Date: 2010-04-15 Impact factor: 21.405
Authors: Annette T Hastie; Wendy C Moore; Deborah A Meyers; Penny L Vestal; Huashi Li; Stephen P Peters; Eugene R Bleecker Journal: J Allergy Clin Immunol Date: 2010-04-15 Impact factor: 10.793
Authors: Wendy C Moore; Deborah A Meyers; Sally E Wenzel; W Gerald Teague; Huashi Li; Xingnan Li; Ralph D'Agostino; Mario Castro; Douglas Curran-Everett; Anne M Fitzpatrick; Benjamin Gaston; Nizar N Jarjour; Ronald Sorkness; William J Calhoun; Kian Fan Chung; Suzy A A Comhair; Raed A Dweik; Elliot Israel; Stephen P Peters; William W Busse; Serpil C Erzurum; Eugene R Bleecker Journal: Am J Respir Crit Care Med Date: 2009-11-05 Impact factor: 21.405
Authors: Mats W Johansson; Elizabeth A B Kelly; William W Busse; Nizar N Jarjour; Deane F Mosher Journal: J Immunol Date: 2008-06-01 Impact factor: 5.422
Authors: Ena Ray Banerjee; Yi Jiang; William R Henderson; Yvette Latchman; Thalia Papayannopoulou Journal: Exp Hematol Date: 2009-06 Impact factor: 3.084
Authors: Mats W Johansson; Stanley J Kruger; Mark L Schiebler; Michael D Evans; Ronald L Sorkness; Loren C Denlinger; William W Busse; Nizar N Jarjour; Robert R Montgomery; Deane F Mosher; Sean B Fain Journal: Am J Respir Crit Care Med Date: 2013-07-15 Impact factor: 21.405
Authors: Bradford A Youngblood; Emily C Brock; John Leung; Rustom Falahati; Bruce S Bochner; Henrik S Rasmussen; Kathryn Peterson; Christopher Bebbington; Nenad Tomasevic Journal: JCI Insight Date: 2019-10-03
Authors: M W Johansson; K A Gunderson; E A B Kelly; L C Denlinger; N N Jarjour; D F Mosher Journal: Clin Exp Allergy Date: 2013-03 Impact factor: 5.018
Authors: Mats W Johansson; Elizabeth A Kelly; Christopher L Nguyen; Nizar N Jarjour; Bruce S Bochner Journal: Int Arch Allergy Immunol Date: 2018-06-07 Impact factor: 2.749