Collagen receptors α1β1 and α2β1 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 α4 and β2 subunits. we hypothesized that also collagen receptors: α1β1 and α2β1,may be involved in cell migration to the inflammatory site in asthma. the aim of the study was to determine whether the inhibition of α1β1 or α2β1 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 α1β1 and α2β1 integrins,respectively) as well as vlo4 (a non-selective inhibitor of α4β1,α5β1 and αvβ3 - 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 α1β1 and α2β1 are likely to be involved in eosinophil transmigration to the inflammatory site. the role of α2β1 on lymphocytes is probably different. as the α2β1 integrin has been described as a stimulator of collagen accumulation,it might be,at least in part,responsible for asthma airway remodelling.