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Glycosaminoglycan Interactions with Chemokines Add Complexity to a Complex System.

ABSTRACT: Chemokines have two types of interactions that function cooperatively to control cell migration. Chemokine receptors on migrating cells integrate signals initiated upon chemokine binding to promote cell movement. Interactions with glycosaminoglycans (GAGs) localize chemokines on and near cell surfaces and the extracellular matrix to provide direction to the cell movement. The matrix of interacting chemokine-receptor partners has been known for some time, precise signaling and trafficking properties of many chemokine-receptor pairs have been characterized, and recent structural information has revealed atomic level detail on chemokine-receptor recognition and activation. However, precise knowledge of the interactions of chemokines with GAGs has lagged far behind such that a single paradigm of GAG presentation on surfaces is generally applied to all chemokines. This review summarizes accumulating evidence which suggests that there is a great deal of diversity and specificity in these interactions, that GAG interactions help fine-tune the function of chemokines, and that GAGs have other roles in chemokine biology beyond localization and surface presentation. This suggests that chemokine-GAG interactions add complexity to the already complex functions of the receptors and ligands.

SUBMITTER: Proudfoot AEI

PROVIDER: S-EPMC5620614 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Glycosaminoglycan Interactions with Chemokines Add Complexity to a Complex System.

Proudfoot Amanda E I AEI Johnson Zoë Z Bonvin Pauline P Handel Tracy M TM

Pharmaceuticals (Basel, Switzerland) 20170809 3

Chemokines have two types of interactions that function cooperatively to control cell migration. Chemokine receptors on migrating cells integrate signals initiated upon chemokine binding to promote cell movement. Interactions with glycosaminoglycans (GAGs) localize chemokines on and near cell surfaces and the extracellular matrix to provide direction to the cell movement. The matrix of interacting chemokine-receptor partners has been known for some time, precise signaling and trafficking propert ...[more]

PMID: 28792472

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Project description:BackgroundThe concept of complexity is used in palliative care (PC) to describe the nature of patients' situations and the extent of resulting needs and care demands. However, the term or concept is not clearly defined and operationalised with respect to its particular application in PC. As a complex problem, a care situation in PC is characterized by reciprocal, nonlinear relations and uncertainties. Dealing with complex problems necessitates problem-solving methods tailored to specific situations. The theory of complex adaptive systems (CAS) provides a framework for locating problems and solutions. This study aims to describe criteria contributing to complexity of PC situations from the professionals' view and to develop a conceptual framework to improve understanding of the concept of "complexity" and related elements of a PC situation by locating the complex problem "PC situation" in a CAS.MethodsQualitative interview study with 42 semi-structured expert (clinical/economical/political) interviews. Data was analysed using the framework method. The thematic framework was developed inductively. Categories were reviewed, subsumed and connected considering CAS theory.ResultsThe CAS of a PC situation consists of three subsystems: patient, social system, and team. Agents in the "system patient" are allocated to further subsystems on patient level: physical, psycho-spiritual, and socio-cultural. The "social system" and the "system team" are composed of social agents, who affect the CAS as carriers of characteristics, roles, and relationships. Environmental factors interact with the care situation from outside the system. Agents within subsystems and subsystems themselves interact on all hierarchical system levels and shape the system behaviour of a PC situation.ConclusionsThis paper provides a conceptual framework and comprehensive understanding of complexity in PC. The systemic view can help to understand and shape situations and dynamics of individual care situations; on higher hierarchical level, it can support an understanding and framework for the development of care structures and concepts. The framework provides a foundation for the development of a model to differentiate PC situations by complexity of patients and care needs. To enable an operationalisation and classification of complexity, relevant outcome measures mirroring the identified system elements should be identified and implemented in clinical practice.

Dataset Information

Glycosaminoglycan Interactions with Chemokines Add Complexity to a Complex System.

Publications

Glycosaminoglycan Interactions with Chemokines Add Complexity to a Complex System.

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