Concurrency in leukocyte vascular recognition: developing the tools for a predictive computer model.

Abstract Leukocyte recruitment has a crucial role in inflammation and immunity. An interplay between adhesion molecules and pro-adhesive agonists generates a complex molecular network controlling tissue-specific and inflammation-dependent leukocyte vascular recognition. Recent findings highlight the importance of quantitative parameters in controlling the specificity of leukocyte vascular recognition. Introduction of quantitative parameters demonstrates the non-linear behavior of the process and suggests the necessity for a revision of the traditional model. We propose a formalization of the original multi-step model of leukocyte vascular recognition by introducing the notion of concurrency that explains how the quantitative variation of pro-adhesive parameters might control the specificity and the sensitivity of this process. Moreover, we discuss how concurrency, by integrating quantitative parameters, constitutes a central concept for the implementation of a predictive computer modeling of leukocyte vascular recognition.

[1]  A. Zlotnik,et al.  The biology of chemokines and their receptors. , 2000, Annual review of immunology.

[2]  James J. Campbell,et al.  The chemokine receptor CCR4 in vascular recognition by cutaneous but not intestinal memory T cells , 1999, Nature.

[3]  L. Picker,et al.  Lymphocyte Homing and Homeostasis , 1996, Science.

[4]  Robin Milner,et al.  A Calculus of Mobile Processes, II , 1992, Inf. Comput..

[5]  Paola Lecca,et al.  A Biospi Model of Lymphocyte-Endothelial Interactions in Inflamed Brain Venules , 2004, Pacific Symposium on Biocomputing.

[6]  E. Butcher,et al.  Lymphocyte trafficking and regional immunity. , 1999, Advances in immunology.

[7]  Mark V. Dahl,et al.  α4 Integrins mediate lymphocyte attachment and rolling under physiologic flow , 1996 .

[8]  A. Mantovani,et al.  The chemokine system: redundancy for robust outputs. , 1999, Immunology today.

[9]  T. Secomb,et al.  Microangiectasias: Structural regulators of lymphocyte transmigration , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Paola Lecca,et al.  Predicting cell adhesion probability via the biochemical stochastic π-calculus , 2004, SAC '04.

[11]  Robin Milner,et al.  Communicating and mobile systems - the Pi-calculus , 1999 .

[12]  R. Pardi,et al.  Localization of Th-cell subsets in inflammation: differential thresholds for extravasation of Th1 and Th2 cells. , 2000, Immunology today.

[13]  E. Butcher,et al.  Chemokines and the arrest of lymphocytes rolling under flow conditions. , 1998, Science.

[14]  Aviv Regev,et al.  Representation and Simulation of Biochemical Processes Using the pi-Calculus Process Algebra , 2000, Pacific Symposium on Biocomputing.

[15]  H. Soto,et al.  CCL27–CCR10 interactions regulate T cell–mediated skin inflammation , 2002, Nature Medicine.

[16]  Corrado Priami,et al.  Application of a stochastic name-passing calculus to representation and simulation of molecular processes , 2001, Inf. Process. Lett..

[17]  W. Somers,et al.  Insights into the Molecular Basis of Leukocyte Tethering and Rolling Revealed by Structures of P- and E-Selectin Bound to SLeX and PSGL-1 , 2000, Cell.

[18]  S. Jalkanen,et al.  How do lymphocytes know where to go: current concepts and enigmas of lymphocyte homing. , 1997, Advances in immunology.

[19]  C. Mackay,et al.  Biology of chemokine and classical chemoattractant receptors: differential requirements for adhesion-triggering versus chemotactic responses in lymphoid cells , 1996, The Journal of cell biology.

[20]  James J. Campbell,et al.  CC Chemokine Receptor (CCR)4 and the CCR10 Ligand Cutaneous T Cell–attracting Chemokine (CTACK) in Lymphocyte Trafficking to Inflamed Skin , 2001, The Journal of experimental medicine.

[21]  Corrado Priami,et al.  Stochastic pi-Calculus , 1995, Comput. J..

[22]  D. Walker,et al.  A Calculus of Mobile Processes, Part Ii , 1989 .

[23]  Carlo Laudanna,et al.  Rapid leukocyte integrin activation by chemokines , 2002, Immunological reviews.

[24]  E. Berg,et al.  α4 integrins mediate lymphocyte attachment and rolling under physiologic flow , 1995, Cell.

[25]  Robin Milner,et al.  Communication and concurrency , 1989, PHI Series in computer science.

[26]  N. Copeland,et al.  CTACK, a skin-associated chemokine that preferentially attracts skin-homing memory T cells. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[27]  S. Cuvelier,et al.  Selectins: critical mediators of leukocyte recruitment. , 2002, Seminars in immunology.

[28]  E. Butcher,et al.  Chemokines in tissue-specific and microenvironment-specific lymphocyte homing. , 2000, Current opinion in immunology.

[29]  Paola Lecca,et al.  A Stochastic Process Algebra Approach to Simulation of Autoreactive Lymphocyte Recruitment , 2004, Simul..

[30]  T. Springer.  Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm , 1994, Cell.

[31]  P. Allavena,et al.  Vasodilation in multistep paradigm of leucocyte extravasation , 1994, The Lancet.

[32]  Giampiero Girolomoni,et al.  Quantitative Differences in Chemokine Receptor Engagement Generate Diversity in Integrin-Dependent Lymphocyte Adhesion1 , 2002, The Journal of Immunology.

[33]  Weiqi Wang,et al.  Cutting Edge: The Orphan Chemokine Receptor G Protein-Coupled Receptor-2 (GPR-2, CCR10) Binds the Skin-Associated Chemokine CCL27 (CTACK/ALP/ILC)1 , 2000, The Journal of Immunology.

[34]  Amnon Peled,et al.  Subsecond Induction of α4 Integrin Clustering by Immobilized Chemokines Stimulates Leukocyte Tethering and Rolling on Endothelial Vascular Cell Adhesion Molecule 1 under Flow Conditions , 2000, The Journal of experimental medicine.