The adhesion protein vitronectin is associated with extracellular matrices and serves as cofactor for plasminogen-activator inhibitor-1 . Limited proteolysis by plasmin converts vitronectin into defined fragments which are detectable at sites of intlammation and angiogenesis. The loss and gain of binding functions of vitronectin fragments for macromolecular ligands was characterized in the present study. The initially generated 61 -63-kDa vitronectin-( 1 -348)-fragment serves as typical binding component for plasminogen and binding function was lost upon carboxypeptidase B treatment indicating the importance of a C-terminal lysine. Complementary binding sites reside in isolated plasminogen kringles 1-3 (designated angiostatin) as deduced from direct binding and ligand blotting experiments. A synthetic vitronectin-(331 -348)-peptide from the C-terminus of the 61 -63-kDa fragment could mimic plasminogen and angiostatin binding. Also, the immobilized peptide bound tissue plasminogen-activator and mediated plasmin formation, comparable to fibrinogen-derived peptides. The 61 -63-kDa vitronectin fragment was indistinguishable in its adhesive properties to intact vitronectin and bound active but not latent plasminogen-activator inhibitor-1 . Late plasminolysis of vitronectin resulted in the processing of the N-terminal region of the protein with the generation of 42 kDd3S-kDa fragments that had GIy89 as new N-terminus and that were ineffective in promoting cell adhesion. Thus, at sites of cell-matrix interactions which become proteolytically modified by plasmin during inflammatory and angiogenic processes, vitronectin serves as plasminogedangiostatin-binding factor. Due to this differential change in functions particularly at sites of deposition in the vascular system or at wound sites vitronectin is considered to be an important morpho-regulatory factor.Keywords: angiostatin ; plasmin ; vitronectin; adhesion ; proteolysis.The molecular dynamics in stabilization and destabilization of cellular contacts is under strict control in many biological systems as diverse as embryo implantation, histogenesis, angiogenesis, cellular extravasation or tumor metastasis [ 11. Cell-specific hydrolytic enzymes and the plasminogen-activation system have been implicated in many instances as modulators of the cell-matrix micro-environment. Thus, cell migration, invasion and cell proliferation rely on a proteolytic/anti-proteolytic balance based on cell-surface-restricted reactions. In particular, cell surface receptors for urokinase [2], tissue plasminogen activator 131 or cellular binding sites for plasminogen [4] are positioned for localized generation of plasmin. The early phase of plasminogen activation is controlled by several serine protease inhibitors of which extracellular matrix-associated plasminogen-activator inhibitor-1 appears to be the predominant one [S]. The multifunctional adhesive protein vitronectin serves as binding and stabilization factor for plasminogen-activator inhibitor-1 [6 -XI, and colocalization of both compo...

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The connection between Pediatric Inflammatory Multisystem Syndrome (PIMS) and Kawasaki Disease (KD) is not yet fully understood. Using the same national registry, clinical features and outcome of children hospitalized in Germany, and Innsbruck (Austria) were compared. Reported to the registry were 395 PIMS and 69 KD hospitalized patients. Patient age in PIMS cases was higher than in KD cases (median 7 [IQR 4–11] vs. 3 [IQR 1–4] years). A majority of both PIMS and KD patients were male and without comorbidities. PIMS patients more frequently presented with organ dysfunction, with the gastrointestinal (80%), cardiovascular (74%), and respiratory (52%) systems being most commonly affected. By contrast, KD patients more often displayed dermatological (99% vs. 68%) and mucosal changes (94% vs. 64%), plus cervical lymph node swelling (51% vs. 34%). Intensive care admission (48% vs. 19%), pulmonary support (32% vs. 10%), and use of inotropes/vasodilators (28% vs. 3%) were higher among PIMS cases. No patients died. Upon patient discharge, potentially irreversible sequelae—mainly cardiovascular—were reported (7% PIMS vs. 12% KD). Despite differences in age distribution and disease severity, PIMS and KD cases shared many common clinical and prognostic characteristics. This supports the hypothesis that the two entities represent a syndrome continuum.