Collagen receptors α(1)β(1) and α(2)β(1) integrins are involved in transmigration of peripheral blood eosinophils, but not mononuclear cells through human microvascular endothelial cells monolayer.
Asthma development may be driven by T helper lymphocytes with eosinophils playing the role of major effector cells. Recruitment of the inflammatory cells from blood to the airways is mediated by adhesive molecules, e.g. selectins and integrins. The most important in cell trafficking are integrins containing α(4) and β(2) subunits. We hypothesized that also collagen receptors: α(1)β(1) and α(2)β(1), may be involved in cell migration to the inflammatory site in asthma. The aim of the study was to determine whether the inhibition of α(1)β(1) or α(2)β(1) integrins, affects transmigration of eosinophils and peripheral blood mononuclear cells (PBMC) through human microvascular endothelial cells monolayer (HMVEC) seeded on collagen IV coated wells in moderate persistent atopic asthmatics.


METHODS
PBMC from 9 asthmatics were separated by gradient centrifugation followed by negative magnetic separation of eosinophils. Snake venom derived anti-adhesive proteins: viperistatin and VP12 (potent and selective inhibitors of α(1)β(1) and α(2)β(1) integrins, respectively) as well as VLO4 (a non-selective inhibitor of α(4)β(1), α(5)β(1) and α(v)β(3) - used as a positive control), were used for inhibition studies. All anti-adhesive proteins studied, inhibited eosinophils, but only VLO4 affected PBMC transmigration through HMVEC. In bronchial asthma both collagen receptors α(1)β(1) and α(2)β(1) are likely to be involved in eosinophil transmigration to the inflammatory site. The role of α(2)β(1) on lymphocytes is probably different. As the α(2)β(1) integrin has been described as a stimulator of collagen accumulation, it might be, at least in part, responsible for asthma airway remodelling.
Second Department of Internal Medicine, Unit of Allergy and Clinical Immunology, Jagiellonian University Medical College, Cracow Poland. mmsocha@cyf-kr.edu.pl
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Bazan-Socha
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Zuk
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Plutecka
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Marcinkiewicz
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Zareba
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Musial
D000328:Adult; D002460:Cell Line; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D039222:Integrin alpha1beta1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D038982:Integrin alpha2beta1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology; D008297:Male; D055806:Microvessels / Q000502:physiology; D012910:Snake Venoms / Q000494:pharmacology; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects / Q000502:physiology*
D039222:Integrin alpha1beta1; D038982:Integrin alpha2beta1; D012910:Snake Venoms