Chemokine activity

About: Chemokine activity is a research topic. Over the lifetime, 223 publications have been published within this topic receiving 9413 citations.

Chemokines in pathology and medicine.

Abstract: About 50 human chemokines and nearly 20 receptors have been identified and characterized in little more than a decade since the discovery of interleukin 8 (IL-8), the first chemotactic cytokine. Research in this field has dramatically changed our understanding of leucocyte traffic in inflammation and immunity. This paper has been written for scientists and practitioners in the field of medicine. It reviews in concise and intelligible form information that I consider useful for understanding the role of chemokines in human pathophysiology. The main areas covered are: (i) the basics of chemokine structures, mode of action, activities and selectivity; (ii) newer aspects of the broad involvement of chemokines in the regulation of immune defence and the housekeeping of the immune system; (iii) the role of chemokines in pathology as illustrated by animal models and studies of human diseases; and (iv) novel therapeutic approaches for a variety of inflammatory conditions, which are based on modulation of chemokine activity.

Role of chemokines in CNS health and pathology: a focus on the CCL2/CCR2 and CXCL8/CXCR2 networks

Abstract: Chemokines and their receptors have crucial roles in the trafficking of leukocytes, and are of particular interest in the context of the unique immune responses elicited in the central nervous system (CNS). The chemokine system CC ligand 2 (CCL2) with its receptor CC receptor 2 (CCR2), as well as the receptor CXCR2 and its multiple ligands CXCL1, CXCL2 and CXCL8, have been implicated in a wide range of neuropathologies, including trauma, ischemic injury and multiple sclerosis. This review aims to overview the current understanding of chemokines as mediators of leukocyte migration into the CNS under neuroinflammatory conditions. We will specifically focus on the involvement of two chemokine networks, namely CCL2/CCR2 and CXCL8/CXCR2, in promoting macrophage and neutrophil infiltration, respectively, into the lesioned parenchyma after focal traumatic brain injury. The constitutive brain expression of these chemokines and their receptors, including their recently identified roles in the modulation of neuroprotection, neurogenesis, and neurotransmission, will be discussed. In conclusion, the value of evidence obtained from the use of Ccl2- and Cxcr2-deficient mice will be reported, in the context of potential therapeutics inhibiting chemokine activity which are currently in clinical trial for various inflammatory diseases.

Directional tissue migration through a self-generated chemokine gradient

Abstract: It is widely accepted that migrating cells and tissues navigate along pre-patterned chemoattractant gradients; here it is shown that migrating tissues can also determine their own direction by generating local gradients of chemokine activity, via polarized receptor-mediated internalization, that are sufficient to ensure robust collective migration. The currently accepted view of how cells migrate directionally over long distances — an important driving force in embryogenesis — is that they navigate using pre-patterned chemoattractant guidance gradients. In this study Darren Gilmour and colleagues present the first in vivo evidence for a rather different mechanism: self-generated guidance gradient formation. Using zebrafish lateral line primordium as a model for collective cell migration, the authors show that migrating tissues can determine their own direction by generating local gradients in initially uniform extracellular guidance cues, producing a travelling wave. The atypical chemokine receptor Cxcr7 is the key regulator of the process, being both necessary and sufficient for self-directed migration. The finding that cells can autonomously determine their migration routes could have wider implications in processes such as cancer metastasis. The directed migration of cell collectives is a driving force of embryogenesis1,2,3. The predominant view in the field is that cells in embryos navigate along pre-patterned chemoattractant gradients2. One hypothetical way to free migrating collectives from the requirement of long-range gradients would be through the self-generation of local gradients that travel with them4,5, a strategy that potentially allows self-determined directionality. However, a lack of tools for the visualization of endogenous guidance cues has prevented the demonstration of such self-generated gradients in vivo. Here we define the in vivo dynamics of one key guidance molecule, the chemokine Cxcl12a, by applying a fluorescent timer approach to measure ligand-triggered receptor turnover in living animals. Using the zebrafish lateral line primordium as a model, we show that migrating cell collectives can self-generate gradients of chemokine activity across their length via polarized receptor-mediated internalization. Finally, by engineering an external source of the atypical receptor Cxcr7 that moves with the primordium, we show that a self-generated gradient mechanism is sufficient to direct robust collective migration. This study thus provides, to our knowledge, the first in vivo proof for self-directed tissue migration through local shaping of an extracellular cue and provides a framework for investigating self-directed migration in many other contexts including cancer invasion6.