Functional Analysis Of Intravital Two-photon Cell Motility Data

Autor: Marc Thilo Figge, Michael Meyer-Hermann
Jazyk: angličtina
Předmět:
Zdroj: Biophysical Journal. (3):626a
ISSN: 0006-3495
DOI: 10.1016/j.bpj.2008.12.3309
Popis: Intravital two-photon microscopy is a powerful tool which allows to observe cell migration and interaction in living tissue. Recently this method was applied to lymphocytes in lymph nodes. The motility of lymphocytes has important implications on the functionality of immune responses. Different cell types entering and leaving lymphoid tissue have to home to their respective compartments and to find suitable interaction partners. Both processes crucially depend on chemotaxis which is mediated by corresponding chemokines and membrane bound receptors. While this knowledge was based on corresponding block- or knock-out-experiments, the aim of the recent two-photon experiments was to clarify the migration mode of lymphocytes in vivo under realistic conditions.Surprisingly two-photon experiments of lymphocyte motility in lymph nodes do not exhibit any sign of chemotactic activity. Three groups have found that the cells basically move in a random walk with directional persistence of 2 minutes (Schwickert etal Nature 2007 446:83; Allen etal Science 2007 315:528; Hauser etal Immunity 2007 26:655). These results induced a controversial discussion about functional implications that could not be resolved on the basis of the measured data alone. We show that a mathematical analysis of cell motility can clarify the interpretation of two-photon motility data for this specific case and in general. Data about tissue morphology and functionality are used together with a simulation of lymphocyte motility to understand the details of chemotaxis in lymphoid compartments. It is found that the chemotactic sensitivity of lymphocytes is tightly regulated and the simulations predict a frequent up and down regulation of chemokine receptors on the plasma membrane. It is shown that under these conditions both the motility data and lymphocyte functionality can be reconciled.
Databáze: OpenAIRE