Journal
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
Volume 45, Issue 4, Pages 889-897Publisher
AMER THORACIC SOC
DOI: 10.1165/rcmb.2010-0402OC
Keywords
eosinophils; adhesion molecules; integrins; P-selectin; cell adhesion
Funding
- National Institutes of Health [P50 HL56396, P01 HL88594, P01 HL88594-02S1, R01 HL80412, M01 RR03186, UL1 RR25011]
- Graduate School, University of Wisconsin-Madison
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Activation of beta(1) integrins of blood eosinophils, assessed by mAb N29, correlates inversely with FEV1 in two paradigms for studying control of human asthma. We asked whether P-selectin causes eosinophil beta(1) integrin activation and results in increased adhesivity. By dual-label flow cytometry, eosinophils with high levels of surface-associated P-selectin had higher reactivity with the activation-sensitive anti-beta(1) mAbs N29, 8E3, and 9EG7 than eosinophils with no or with a low-level of surface-associated P-selectin. Among patients with non-severe asthma, surface P-selectin correlated with N29, 8E3, and 9EG7 signals. By immunofluorescence microscopy, surface-associated P-selectin was present in patches on eosinophils, some of which stained for the platelet marker thrombospondin-1. Activated beta(1) and P-selectin partially colocalized on eosinophils. Soluble P-selectin added to whole blood enhanced activation of eosinophil beta(1), but not beta(2), integrins. In contrast, IL-5 activated eosinophil beta(2), but not beta(1), integrins. Eosinophils that did not attach to vascular cell adhesion molecule-1 (VCAM-1) in a static adhesion assay had a lower N29 signal than the original population. Soluble P-selectin added to whole blood enhanced eosinophil adhesion to VCAM-1. These findings are compatible with a scenario whereby P-selectin, on eosinophil-associated activated platelets or acquired from plasma or from prior interactions with endothelial cells or platelets, activates eosinophil alpha(4)beta(1) integrin and stimulates eosinophils to adhere to VCAM-1 and move to the airway in asthma.
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