Adhesion Molecules: The Path to a New Understanding of Acute Inflammation

Physiology ◽  
2000 ◽  
Vol 15 (3) ◽  
pp. 107-113 ◽  
Author(s):  
Barbara Walzog ◽  
Peter Gaehtgens
Keyword(s):  
Inflammatory Response ◽  
Adhesion Molecules ◽  
Acute Inflammation ◽  
Molecular Mechanisms ◽  
Leukocyte Recruitment ◽  
Basic Principles ◽  
Leukocyte Extravasation ◽  
Definition Of

About 100 years after the definition of the basic principles of inflammation, the identification of the underlying molecular mechanisms provides a new understanding of the inflammatory response. The specificity and diversity of the adhesion molecules involved in leukocyte extravasation account for the ordered leukocyte recruitment and activation in inflammation.

scholarly journals Role and Molecular Mechanisms of Pericytes in Regulation of Leukocyte Diapedesis in Inflamed Tissues

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Paulina Rudziak ◽  
Christopher G. Ellis ◽  
Paulina M. Kowalewska
Keyword(s):  
Basement Membrane ◽  
Matrix Protein ◽  
Molecular Mechanisms ◽  
Leukocyte Recruitment ◽  
Extracellular Matrix Protein ◽  
Chemotactic Migration ◽  
Blood Vessel Formation ◽  
Vascular Basement Membrane ◽  
Leukocyte Extravasation

Leukocyte recruitment is a hallmark of the inflammatory response. Migrating leukocytes breach the endothelium along with the vascular basement membrane and associated pericytes. While much is known about leukocyte-endothelial cell interactions, the mechanisms and role of pericytes in extravasation are poorly understood and the classical paradigm of leukocyte recruitment in the microvasculature seldom adequately discusses the involvement of pericytes. Emerging evidence shows that pericytes are essential players in the regulation of leukocyte extravasation in addition to their functions in blood vessel formation and blood-brain barrier maintenance. Junctions between venular endothelial cells are closely aligned with extracellular matrix protein low expression regions (LERs) in the basement membrane, which in turn are aligned with gaps between pericytes. This forms preferential paths for leukocyte extravasation. Breaching of the layer formed by pericytes and the basement membrane entails remodelling of LERs, leukocyte-pericyte adhesion, crawling of leukocytes on pericyte processes, and enlargement of gaps between pericytes to form channels for migrating leukocytes. Furthermore, inflamed arteriolar and capillary pericytes induce chemotactic migration of leukocytes that exit postcapillary venules, and through direct pericyte-leukocyte contact, they induce efficient interstitial migration to enhance the immunosurveillance capacity of leukocytes. Given their role as regulators of leukocyte extravasation, proper pericyte function is imperative in inflammatory disease contexts such as diabetic retinopathy and sepsis. This review summarizes research on the molecular mechanisms by which pericytes mediate leukocyte diapedesis in inflamed tissues.

scholarly journals Organ Damage in Sepsis: Molecular Mechanisms

2021 ◽  
Author(s):  
Grażyna Sygitowicz ◽  
Dariusz Sitkiewicz
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Molecular Mechanisms ◽  
Cell Metabolism ◽  
Organ Damage ◽  
Antioxidant Systems ◽  
Vascular Endothelial ◽  
Altered Expression ◽  
Non Coding Rna ◽  
Definition Of

Sepsis is one of the most common reasons for hospitalisation. This condition is characterised by systemic inflammatory response to infection. International definition of sepsis mainly points out a multi-organ dysfunction caused by a deregulated host response to infection. An uncontrolled inflammatory response, often referred to as “cytokine storm”, leads to an increase in oxidative stress as a result of the inhibition of cellular antioxidant systems. Oxidative stress, as well as pro-inflammatory cytokines, initiate vascular endothelial dysfunction and, in consequence, impair microcirculation. Microcirculation damage leads to adaptive modifications of cell metabolism. Moreover, mitochondrial dysfunction takes place which results in increased apoptosis and impaired autophagy. Non-coding RNA, especially miRNA and lncRNA molecules, may play an important role in the pathomechanism of sepsis. Altered expression of various ncRNAs in sepsis suggest, that these molecules can be used not only as diagnostics and prognostic markers but also as the target points in the pharmacotherapy of sepsis. The understanding of detailed molecular mechanisms leading to organ damage can contribute to the development of specific therapy methods thereby improving the prognosis of patients with sepsis.

Melatonin: Protection of the Intervertebral Disc

2019 ◽  
Vol 2 (3) ◽  
pp. 1-9
Author(s):  
Russel J Reiter ◽  
Sergio Rosales-Corral ◽  
Ramaswamy Sharma
Keyword(s):  
Intervertebral Disc ◽  
Molecular Mechanisms ◽  
Intervertebral Discs ◽  
Lumbar Pain ◽  
Low Back ◽  
Work Time ◽  
Protective Actions ◽  
Aging Populations ◽  
Definition Of ◽  
Endogenous Melatonin

     Low back pain (lumbar pain) due to injury of or damage to intervertebral discs is common in all societies.  The loss of work time as a result of this problem is massive.  Recent research suggests that melatonin may prevent or counteract intervertebral disc damage. This may be especially relevant in aging populations given that endogenous melatonin, in most individuals, dwindles with increasing age. The publications related to melatonin and its protection of the intervertebral disc are reviewed herein, including definition of some molecular mechanisms that account for melatonin’s protective actions. 

Relationship Between Gamma-glutamyl Transpeptidase Activity and Inflammatory Response in Lichen Planus

2018 ◽  
Vol 69 (3) ◽  
pp. 739-743 ◽  
Author(s):  
Madalina Irina Mitran ◽  
Ilinca Nicolae ◽  
Corina Daniela Ene ◽  
Cristina Iulia Mitran ◽  
Clara Matei ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Lichen Planus ◽  
Inflammatory Process ◽  
Molecular Mechanisms ◽  
Functional Adaptation ◽  
Physical Factors ◽  
Inflammatory Disorder ◽  
Gamma Glutamyl Transpeptidase ◽  
Gamma Glutamyl ◽  
Glutamyl Transpeptidase

Chemicals used in the manufacture of synthetic fibers have been associated with undesirable side effects such as itching or skin lesions and it seems that they are involved in the induction of pathological processes such as oxidative stress and inflammation. Lichen planus (LP) can be regarded as an inflammatory disorder, chemical and physical factors playing an important role in the perpetuation of the inflammatory process. Gamma-glutamyl transpeptidase (GGT) plays an important role in the preservation of skin architecture and modulation of skin inflammation. In this study, we found that GGT activity is increased in LP patients with mild inflammation, whilst GGT is inactivated under conditions of severe inflammation. Therefore, GGT is involved in the inflammatory process, but there is no a positive correlation between its activity and the intensity of the inflammatory response. This functional adaptation of the enzyme may be due to down-regulation of its synthesis under free radical overload conditions. Understanding the molecular mechanisms involved in the modulation of intracellular redox homeostasis is an important step in the pharmacological management of patients with LP.

Toxicology

2017 ◽  
Author(s):  
Robert Laumbach ◽  
Michael Gochfeld
Keyword(s):  
Molecular Mechanisms ◽  
Molecular Targets ◽  
Toxicity Testing ◽  
The Body ◽  
Toxic Substances ◽  
Basic Principles ◽  
Practical Applications ◽  
Mechanisms Of Toxicity ◽  
Body Distribution ◽  
Threshold Doses

This chapter describes the basic principles of toxicology and their application to occupational and environmental health. Topics covered include pathways that toxic substances may take from sources in the environment to molecular targets in the cells of the body where toxic effects occur. These pathways include routes of exposure, absorption into the body, distribution to organs and tissues, metabolism, storage, and excretion. The various types of toxicological endpoints are discussed, along with the concepts of dose-response relationships, threshold doses, and the basis of interindividual differences and interspecies differences in response to exposure to toxic substances. The diversity of cellular and molecular mechanisms of toxicity, including enzyme induction and inhibition, oxidative stress, mutagenesis, carcinogenesis, and teratogenesis, are discussed and the chapter concludes with examples of practical applications in clinical evaluation and in toxicity testing.

scholarly journals Poldip2 controls leukocyte infiltration into the ischemic brain by regulating focal adhesion kinase-mediated VCAM-1 induction

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lori N. Eidson ◽  
Qingzeng Gao ◽  
Hongyan Qu ◽  
Daniel S. Kikuchi ◽  
Ana Carolina P. Campos ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cerebral Ischemia ◽  
Focal Adhesion Kinase ◽  
Adhesion Molecules ◽  
Focal Adhesion ◽  
Vascular Inflammation ◽  
Leukocyte Recruitment ◽  
Ischemic Brain ◽  
Inflammatory Monocytes

AbstractStroke is a multiphasic process involving a direct ischemic brain injury which is then exacerbated by the influx of immune cells into the brain tissue. Activation of brain endothelial cells leads to the expression of adhesion molecules such vascular cell adhesion molecule 1 (VCAM-1) on endothelial cells, further increasing leukocyte recruitment. Polymerase δ-interacting protein 2 (Poldip2) promotes brain vascular inflammation and leukocyte recruitment via unknown mechanisms. This study aimed to define the role of Poldip2 in mediating vascular inflammation and leukocyte recruitment following cerebral ischemia. Cerebral ischemia was induced in Poldip2+/+ and Poldip2+/− mice and brains were isolated and processed for flow cytometry or RT-PCR. Cultured rat brain microvascular endothelial cells were used to investigate the effect of Poldip2 depletion on focal adhesion kinase (FAK)-mediated VCAM-1 induction. Poldip2 depletion in vivo attenuated the infiltration of myeloid cells, inflammatory monocytes/macrophages and decreased the induction of adhesion molecules. Focusing on VCAM-1, we demonstrated mechanistically that FAK activation was a critical intermediary in Poldip2-mediated VCAM-1 induction. In conclusion, Poldip2 is an important mediator of endothelial dysfunction and leukocyte recruitment. Thus, Poldip2 could be a therapeutic target to improve morbidity following ischemic stroke.

scholarly journals International law protecting the environment during armed conflict: gaps and opportunities

2010 ◽  
Vol 92 (879) ◽  
pp. 569-592 ◽  
Author(s):  
Michael Bothe ◽  
Carl Bruch ◽  
Jordan Diamond ◽  
David Jensen
Keyword(s):  
International Law ◽  
Armed Conflict ◽  
Environmental Law ◽  
International Humanitarian Law ◽  
Environmental Damage ◽  
Humanitarian Law ◽  
International Environmental Law ◽  
Basic Principles ◽  
Principle Of Proportionality ◽  
Definition Of

AbstractThere are three key deficiencies in the existing body of international humanitarian law (IHL) relating to protection of the environment during armed conflict. First, the definition of impermissible environmental damage is both too restrictive and unclear; second, there are legal uncertainties regarding the protection of elements of the environment as civilian objects; and third, the application of the principle of proportionality where harm to the environment constitutes ‘collateral damage’ is also problematic. These gaps present specific opportunities for clarifying and developing the existing framework. One approach to addressing some of the inadequacies of IHL could be application of international environmental law during armed conflict. The detailed norms, standards, approaches, and mechanisms found in international environmental law might also help to clarify and extend basic principles of IHL to prevent, address, or assess liability for environmental damage incurred during armed conflict.

An Interaction Between Genetic Factors and Gender Determines the Magnitude of the Inflammatory Response in the Mouse Air Pouch Model of Acute Inflammation

Inflammation ◽  
2005 ◽  
Vol 29 (1) ◽  
pp. 1-7 ◽  
Author(s):  
David L. Delano ◽  
M. Carmen Montesinos ◽  
Peter D'Eustachio ◽  
Tim Wiltshire ◽  
Bruce N. Cronstein
Keyword(s):  
Inflammatory Response ◽  
Acute Inflammation ◽  
Genetic Factors ◽  
Air Pouch ◽  
And Gender ◽  
Air Pouch Model
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