technical report Rate sensitivity analysis of a Beta binders model of lymphocyte recruitment control mechanism


The interaction between lymphocyte in the circulation and endothelial cells lining the blood vessels is a crucial control point in the mechanism of chemotactic detection of inflammation sites. This interaction is mediated by a multisptep process, termed lymphocyte recruit ment, involving lymphocyte rolling along the endothelium, activation of lymphocyte integrins, adhesion to endothelial ligands and lymphocyte crossing the endothelium. The events of the lymphocyte extravasation, called diapedesis is crucial in the pathogenesis of autoimmune neurological diseases, like multiple sclerosis. Recent wet-labs studies provided the data and the observations proving that chemokines modulate the control of the lymphocyte-endothelial cell recognition and regulate the arrest of lymphocyte. In this paper we present a model of lymphocyte recruitment expressed in the formalism of beta-binders and we explore its sensitivity in response to changes of the rates of interaction between chemokines and their receptors. The study is motivated by the intention to individuate those ligand/receptor interactions and their kinetic parameters that are significantly influential in determining the firm arrest of the lymphocyte. We focuses the analysis on the rate coefficients of the chemokines interations. By tuning these parameters we estimate the sensitivity of the model to the rapidity of the lymphocyte adhesion, that recent in vivo observations suggest to be an important factor determining the final result of the rolling process.

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P. Lecca,  W. Ooi,  C. Priami