At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, how...

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Free Radicals in the Physiological Control of Cell Function

Rho GTPases are key regulators of cytoskeletal dynamics and affect many cellular processes, including cell polarity, migration, vesicle trafficking and cytokinesis. These proteins are conserved from plants and yeast to mammals, and function by interacting with and stimulating various downstream targets, including actin nucleators, protein kinases and phospholipases. The roles of Rho GTPases have been extensively studied in different mammalian cell types using mainly dominant negative and constitutively active mutants. The recent availability of knockout mice for several members of the Rho family reveals new information about their roles in signalling to the cytoskeleton and in development.

Mammalian Rho GTPases: new insights into their functions from in vivo studies.

Chemokines compose a sophisticated communication system used by all our cell types, including immune cells. Chemokine messages are decoded by specific receptors that initiate signal transduction events leading to a multitude of cellular responses, leukocyte chemotaxis and adhesion in particular. Critical determinants of the in vivo activities of chemokines in the immune system include their presentation by endothelial cells and extracellular matrix molecules, as well as their cellular uptake via "silent" chemokine receptors (interceptors) leading either to their transcytosis or to degradation. These regulatory mechanisms of chemokine histotopography, as well as the promiscuous and overlapping receptor specificities of inflammation-induced chemokines, shape innate responses to infections and tissue damage. Conversely, the specific patterns of homeostatic chemokines, where each chemokine is perceived by a single receptor, are charting lymphocyte navigation routes for immune surveillance. This review presents our current understanding of the mechanisms that regulate the cellular perception and pathophysiologic meaning of chemokines.

Chemokines in Innate and Adaptive Host Defense: Basic Chemokinese Grammar for Immune Cells

Cell migration involves dynamic and spatially regulated changes to the cytoskeleton and cell adhesion. The Rho GTPases play key roles in coordinating the cellular responses required for cell migration. Recent research has revealed new molecular links between Rho family proteins and the actin cytoskeleton, showing that they act to regulate actin polymerization, depolymerization and the activity of actin-associated myosins. In addition, studies on integrin signalling suggest that the substratum continuously feeds signals to Rho proteins in migrating cells to influence migration rate. There is also increasing evidence that Rho proteins affect the organization of the microtubule and intermediate filament networks and that this is important for cell migration.

Rho GTPases and cell migration.

Reactive oxygen and reactive nitrogen intermediates in innate and specific immunity

Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense.

Described are preferred methods for obtaining a hematopoietic cell population having a large percentage of quiescent cells having a desirable engraftment phenotype. Also described are methods for inducing apoptosis in hematopoietic cells. Further described are culture mediums and cell populations useful in and resulting from methods of the invention.

Gillian B. Bradford

Papers

Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense.

Methods for enriching for quiescent cells in hematopoietic cell populations