The migration of inflammatory cells from the peripheral blood to the tissue involves many steps, including chemokinesis, chemotaxis, expression of adhesion molecules, endothelial adherence, and transmigration through the endothelial wall.
13 This final step involves many cellular functions, such as modification of the cell skeleton, diapedesis, and digestion of the extracellular matrix and basement membrane.
14 Candidates for these final steps are the MMP and the plasminogen–plasmin system.
1 15 Plasmin and uPA directly or indirectly hydrolyze extracellular matrix proteins by inducing a cascade of proteolytic events leading to MMP activation. The binding of uPA to its cell-membrane receptor (uPAR) not only increases the rate of plasminogen activation, but also allows this proteolytic process to occur in a focal and spatially oriented manner, as is necessary for cell migration.
4 5 16 This system is known to promote degradation of the extracellular matrix and has been reported in monocytes, T lymphocytes, neutrophils, and eosinophils.
17 18 19 20 21 MMP-9 and the plasminogen–plasmin complex are the two most well-known proteases expressed by eosinophils.
22 23 Increased tear levels of the potent selective eosinophil chemotactic factors, eotaxin-1 and -2, and MMP-9 have been recently described in patients with VKC.
24 25 26 27 These factors correlate with the percentage of eosinophils in tears, suggesting that they are involved in eosinophil chemotaxis and transmigration in VKC. In an in vitro model of eosinophil transmigration through a basement membrane component, eotaxin proved to promote eosinophil transmigration via plasminogen–plasmin activation.
28 In similar studies, the combination of two other eosinophil activators, platelet-activating factors (PAFs) and IL-5, induced eosinophil transmigration by activation of MMP-9 and serine proteases.
15 29