Integrin adhesion receptors are essential for the development and functioning of multicellular animals. Integrins mediate cell adhesion to the extracellular matrix and to counter-receptors on adjacent cells, and the ability of integrins to bind extracellular ligands is regul ...
Focal adhesions (FAs) are discrete plasma membrane-associated adhesive organelles that play dual roles in cell force transduction and signaling. FAs consist of clustered transmembrane heterodimeric integrin extracellular matrix (ECM) receptors and a large number of cytopl ...
In leukocytes, integrins play important roles in adhesive interactions with endothelium, antigen-presenting cells, and effector functions such as cytotoxicity. This chapter describes methods to study Ras proximity 1 (Rap1), a signaling molecule that has been increasingly rec ...
It has been well established that integrins mediate cell–cell and cell–matrix adhesion and play crucial roles in the immune system such as leukocyte–endothelium interactions, immune synapse formation, and effector functions. Since the discovery that integrins undergo dynamic c ...
Intravital microscopy (IVM) allows for the direct in vivo visualization of dynamic biological processes in their physiological context at high spatial and temporal resolution. Novel nonlinear optical imaging modalities, most prominently multiphoton microscopy, have exte ...
Immune system functions rely heavily on the ability of immune cells (i.e., blood leukocyte) to traffic throughout the body as they conduct immune surveillance and respond to pathogens. A monolayer of vascular endothelial cells (i.e., the “endothelium”) provides a critical, selectively p ...
Aberrant integrin activation is associated with several immune pathologies. In leukocyte adhesion deficiency (LAD), the absence or inability of β2 integrins to undergo affinity upregulation contributes to recurrent infectious episodes and impaired wound healing, while exc ...
T-cell motility is critical for leukocyte trafficking both in normal host defense and in pathologic conditions including chronic inflammatory disease. Despite progress in understanding the mechanisms of T-cell polarity and motility, we have limited understanding of the mechan ...
Integrins play critical adhesion and signaling roles during development, wound healing, immunity, and cancer. Central to their function is a unique ability to dynamically modulate their adhesiveness and signaling properties through changes in conformation, both homo- and heter ...
Angiogenesis, the formation of new blood vessel, plays an important role for the growth and metastasis of malignant tumors. The recent identification of specific growth factors for lymphatic vessels and of new lymphatic-specific markers provided evidence for an active role of the lymph ...
Dictyostelium discoideum is an excellent model organism for the study of directed cell migration, since Dictyostelium cells show robust chemotactic responses to the chemoattractant cAMP. Many powerful experimental tools are applicable, including forward and reverse genet ...
Mass spectrometry-based proteomics is a field that has been quickly developing, enabling increasingly giving in-depth characterization of the proteomes of cells and tissues. Current technology allows identifying thousands of proteins in a single experiment. Stable isotope l ...
Effector/memory T cells can migrate to most extra-lymphoid tissues in the body. However, migration to the intestinal mucosa requires the expression of very specific homing receptors on T cells, integrin α4β7 and chemokine receptor CCR9. These receptors are induced by all-trans retinoic ...
The RNA interference (RNAi) and interferons have been an uneasy marriage. Ever since the discovery of RNAi in mammals, the interferon response has been a feared problem. While RNAi became an efficient and widespread method for gene silencing in mammals, numerous studies recognized several ...
Excessive scarring (fibrosis) is a major cause of pathologies in multiple tissues, including lung, liver, kidney, heart, cornea, and skin. The transforming growth factor-β (TGF-β) system has been shown to play a key role in regulating the formation of scar tissue throughout the body. Furthermo ...
Utilizing small interfering RNAs (siRNAs) to silence disease-associated genes holds promise as a potential therapeutic strategy. However, the greatest challenge for RNAi remains the delivery of siRNA to target tissues or cells. Specifically lymphocytes are difficult to transd ...
Cytokine biosynthesis is tightly regulated by a number of processes, including gene expression control. Posttranscriptional control of cytokine gene expression offers a fine-tuning mechanism that contributes not only to transient biosynthesis of cytokines, but also helps in r ...
Humanized mice have recently emerged as powerful translational animal models for studying human hematopoiesis, immune interactions, and diseases of the human immune system. Several important advances in the humanized mouse technology have been reported over the last few years, th ...
Integrins are heterodimeric membrane glycoproteins composed of noncovalently associated α and β subunits. Integrins support cell attachment and migration on the surrounding extracellular matrix as well as mediate cell–cell interaction in physiological and pathological ...
Integrins are involved in a wide range of cell interactions. Imaging their distribution using high-resolution noninvasive techniques that are directly translatable to the clinic can provide new insights into disease processes and presents the opportunity to directly monitor new ...