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British Medical Bulletin Sep 2018Radionuclides for leucocyte kinetic studies have progressed from non-gamma emitting cell-labelling radionuclides through gamma emitting nuclides that allow imaging of... (Review)
Review
INTRODUCTION
Radionuclides for leucocyte kinetic studies have progressed from non-gamma emitting cell-labelling radionuclides through gamma emitting nuclides that allow imaging of leucocyte kinetics, to the next goal of positron emission tomography (PET).
SOURCES OF DATA
Mostly the authors' own studies, following on from studies of the early pioneers.
AREAS OF CONTROVERSY
From early imaging studies, it appeared that the majority of the marginated granulocyte pool was located in the lungs. However, later work disputed this by demonstrating the exquisite sensitivity of granulocytes to ex vivo isolation and labelling, and that excessive lung activity is artefactual.
AREAS OF AGREEMENT
Following refinement of labelling techniques, it was shown that the majority of marginated granulocytes are located in the spleen and bone marrow. The majority of leucocytes have a pulmonary vascular transit time only a few seconds longer than erythrocytes. The minority showing slow transit, ~5% in healthy persons, is increased in systemic inflammatory disorders that cause neutrophil priming and loss of deformability. Using a range of imaging techniques, including gamma camera imaging, whole-body counting and single photon-emission computerized tomography, labelled granulocytes were subsequently used to image pulmonary trafficking in lobar pneumonia, bronchiectasis, chronic obstructive pulmonary disease and adult respiratory distress syndrome.
GROWING POINTS
More recently, eosinophils have been separated in pure form using magnetic bead technology for the study of eosinophil trafficking in asthma.
AREAS TIMELY FOR DEVELOPING RESEARCH
These include advancement of eosinophil imaging, development of monocyte labelling, development of cell labelling with PET tracers and the tracking of lymphocytes.
Topics: Granulocytes; Humans; Isotope Labeling; Leukocytes; Lung Diseases; Positron-Emission Tomography; Radioisotopes
PubMed: 30052802
DOI: 10.1093/bmb/ldy022 -
Cardiovascular Research Aug 2015The functions of blood cells extend well beyond the immune functions of leucocytes or the respiratory and hemostatic functions of erythrocytes and platelets. Seen as a... (Review)
Review
The functions of blood cells extend well beyond the immune functions of leucocytes or the respiratory and hemostatic functions of erythrocytes and platelets. Seen as a whole, the bloodstream is in charge of nurturing and protecting all organs by carrying a mixture of cell populations in transit from one organ to another. To optimize these functions, evolution has provided blood and the vascular system that carries it with various mechanisms that ensure the appropriate influx and egress of cells into and from the circulation where and when needed. How this homeostatic control of blood is achieved has been the object of study for over a century, and although the major mechanisms that govern it are now fairly well understood, several new concepts and mediators have recently emerged that emphasize the dynamism of this liquid tissue. Here we review old and new concepts that relate to the maintenance and regulation of leucocyte homeostasis in blood and briefly discuss the mechanisms for platelets and red blood cells.
Topics: Animals; Blood Circulation; Cell Movement; Cholesterol; Homeostasis; Humans; Leukocytes
PubMed: 25750191
DOI: 10.1093/cvr/cvv099 -
Frontiers in Immunology 2019The lymphatics fulfill a vital physiological function as the conduits through which leucocytes traffic between the tissues and draining lymph nodes for the initiation... (Review)
Review
The lymphatics fulfill a vital physiological function as the conduits through which leucocytes traffic between the tissues and draining lymph nodes for the initiation and modulation of immune responses. However, until recently many of the molecular mechanisms controlling such migration have been unclear. As a result of careful research, it is now apparent that the process is regulated at multiple stages from initial leucocyte entry and intraluminal crawling in peripheral tissue lymphatics, through to leucocyte exit in draining lymph nodes where the migrating cells either participate in immune responses or return to the circulation efferent lymph. Furthermore, it is increasingly evident that most if not all leucocyte populations migrate in lymph and that such migration is not only important for immune modulation, but also for the timely repair and resolution of tissue inflammation. In this article, I review the latest research findings in these areas, arising from new insights into the distinctive ultrastructure of lymphatic capillaries and lymph node sinuses. Accordingly, I highlight the emerging importance of the leucocyte glycocalyx and its novel interactions with the endothelial receptor LYVE-1, the intricacies of endothelial chemokine secretion and sequestration that direct leucocyte trafficking and the significance of the process for normal immune function and pathology.
Topics: Cell Movement; Endothelium, Lymphatic; Humans; Leukocytes; Lymph Nodes; Lymphatic Vessels; Vesicular Transport Proteins
PubMed: 30923528
DOI: 10.3389/fimmu.2019.00471 -
Cells Oct 2022Leukocytes are essential for the function of the immune system and cell-cell interaction in the human body, but hematological diseases as well as chemotherapeutic... (Review)
Review
Leukocytes are essential for the function of the immune system and cell-cell interaction in the human body, but hematological diseases as well as chemotherapeutic treatments due to cancer lead to occasionally or even permanent leukocyte deficiency. Normally, more than 50% of leukocytes are neutrophilic granulocytes, and leukopenia is, therefore, mostly characterized by a decrease in neutrophilic granulocytes. The consequence of neutropenia is increased susceptibility to infection, but also healing disorders are suggestable due to the disturbed cell-cell interaction. While there is no surgical treatment for leucocyte disorders, patients suffering from neutropenia are sometimes in need of surgery for other reasons. Less is known about the morbidity and mortality of this patients, which is why this narrative review critically summarizes the results of recent research in this particular field. The results of this review suggest that neutropenic patients in need of emergency surgery have a higher mortality risk compared to non-neutropenic patients. In contrast, in elective surgery, there was not a clear tendency for a higher mortality risk of neutropenic patients. The role of neutrophilic granulocytes in inflammation and immunity in surgical patients is emphasized by the results, but most of the evaluated studies showed methodological flaws due to small sample sizes or risk of bias. Further research has to evaluate the risk for postoperative complications, particularly of infectious complications such as surgical site infections, in neutropenic patients undergoing elective surgery, and should address the role of neutrophilic function in postoperative morbidity and mortality.
Topics: Humans; Neutropenia; Granulocytes; Morbidity; Leukocytes; Digestive System Surgical Procedures
PubMed: 36291181
DOI: 10.3390/cells11203314 -
Cell Adhesion & Migration 2014Leukocyte transendothelial migration (TEM) is one of the crucial steps during inflammation. A better understanding of the key molecules that regulate leukocyte... (Review)
Review
Leukocyte transendothelial migration (TEM) is one of the crucial steps during inflammation. A better understanding of the key molecules that regulate leukocyte extravasation aids to the development of novel therapeutics for treatment of inflammation-based diseases, such as atherosclerosis and rheumatoid arthritis. The adhesion molecules ICAM-1 and VCAM-1 are known as central mediators of TEM. Clustering of these molecules by their leukocytic integrins initiates the activation of several signaling pathways within the endothelium, including a rise in intracellular Ca (2+), activation of several kinase cascades, and the activation of Rho-GTPases. Activation of Rho-GTPases has been shown to control adhesion molecule clustering and the formation of apical membrane protrusions that embrace adherent leukocytes during TEM. Here, we discuss the potential regulatory mechanisms of leukocyte extravasation from an endothelial point of view, with specific focus on the role of the Rho-GTPases.
Topics: Cell Adhesion; Cell Movement; Endothelial Cells; Humans; Intercellular Adhesion Molecule-1; Leukocytes; Signal Transduction; Transendothelial and Transepithelial Migration; Vascular Cell Adhesion Molecule-1; rho GTP-Binding Proteins
PubMed: 24621576
DOI: 10.4161/cam.28244 -
The Biochemical Journal Jan 2005Leucocytes in the bloodstream respond rapidly to inflammatory signals by crossing the blood vessel wall and entering the tissues. This process involves adhesion to, and... (Review)
Review
Leucocytes in the bloodstream respond rapidly to inflammatory signals by crossing the blood vessel wall and entering the tissues. This process involves adhesion to, and subsequent transmigration across, the endothelium, mediated by a cascade of interactions between adhesion molecules and stimulation of intracellular signalling pathways in both leucocytes and endothelial cells. This leads to changes in endothelial cell morphology that assist leucocyte extravasation, including endothelial cell contraction, intercellular junction disruption, increased permeability, remodelling of the endothelial apical surface and alterations in vesicle trafficking. Rho GTPases play a central role in many of the endothelial responses to leucocyte interaction. In this review, we discuss recent findings on leucocyte-induced alterations to endothelial cells, and the roles of Rho GTPases in these responses.
Topics: Animals; Endothelium; Humans; Leukocytes; rho GTP-Binding Proteins
PubMed: 15496138
DOI: 10.1042/BJ20041584 -
Cardiovascular Research Aug 2015Leucocyte transendothelial migration (TEM) involves a co-operative series of interactions between surface molecules on the leucocyte and cognate counter-ligands on the... (Review)
Review
Leucocyte transendothelial migration (TEM) involves a co-operative series of interactions between surface molecules on the leucocyte and cognate counter-ligands on the endothelial cell. These interactions set up a cascade of signalling events inside the endothelial cell that both allow for the junctions to loosen and for membrane to be recruited from the lateral border recycling compartment (LBRC). The LBRC is thought to provide an increased surface area and unligated receptors to the leucocyte to continue the process. The relative importance of the individual adhesion/signalling molecules that promote transmigration may vary depending on the type of leucocyte, the vascular bed, the inflammatory stimulus, and the stage of the inflammatory response. However, the molecular interactions between leucocyte and endothelial cell activate signalling pathways that disengage the adherens and tight junctions and recruit the LBRC to the site of transmigration. With the exception of disengaging the junctions, similar molecules and mechanisms promote transcellular migration as paracellular migration of leucocytes. This review will discuss the molecular interactions and signalling pathways that regulate transmigration, and the common themes that emerge from studying TEM of different leucocyte subsets under different inflammatory conditions. We will also raise some unanswered questions in need of future research.
Topics: Animals; Endothelial Cells; Humans; Leukocytes; Signal Transduction; Tight Junctions; Transendothelial and Transepithelial Migration
PubMed: 25987544
DOI: 10.1093/cvr/cvv145 -
Cell and Tissue Research Aug 2011The lipidic modification of proteins has recently been shown to be of immense importance, although many of the roles of these modifications remain as yet unidentified.... (Review)
Review
The lipidic modification of proteins has recently been shown to be of immense importance, although many of the roles of these modifications remain as yet unidentified. One of such key modifications occurring on several proteins is the covalent addition of a 14-carbon long saturated fatty acid, a process termed myristoylation. Myristoylation can occur during both co-translational protein synthesis and posttranslationally, confers lipophilicity to protein molecules, and controls protein functions. The protein myristoylation process is catalyzed by the enzyme N-myristoyltransferase (NMT), which exists as two isoforms: NMT1 and NMT2. NMT1 is essential for growth and development, during which rapid cellular proliferation is required, in a variety of organisms. NMT1 is also reported to be elevated in many cancerous states, which also involve rapid cellular growth, albeit in an unwanted and uncontrolled manner. The delineation of myristoylation-dependent cellular functions is still in a state of infancy, and many of the roles of the myristoylated proteins remain to be established. The development of cells of the leukocytic lineage represents a phase of rapid growth and development, and we have observed that NMT1 plays a role in this process. The current review outlines the roles of NMT1 in the growth and differentiation of the cells of leukocytic origin. The described studies clearly demonstrate the roles of NMT1 in the regulation of the developmental processes of the leukocytes cells and provide a basis for further research with the aim of unraveling the roles of protein myristoylation in both cellular and physiological context.
Topics: Acyltransferases; Animals; Cell Growth Processes; Humans; Leukocytes
PubMed: 21698528
DOI: 10.1007/s00441-011-1202-x -
British Journal of Anaesthesia Jul 2008In inflammation, leucocytes containing opioid peptides migrate into the tissue. Opioid peptides can be released and bind to opioid receptors on peripheral nerve... (Review)
Review
In inflammation, leucocytes containing opioid peptides migrate into the tissue. Opioid peptides can be released and bind to opioid receptors on peripheral nerve terminals, which counteracts inflammatory pain. Migration of opioid peptide-containing leucocytes is controlled by chemokines and adhesion molecules. Neurokinins, such as, substance P also contribute to the recruitment of these cells. Opioid peptide release from granulocytes can be stimulated by chemokines, such as, CXCR2 ligands. The release is dependent on intracellular calcium and activation of phosphoinositol-3 kinase and p38 mitogen activated kinase. Endogenous opioid peptides produced by leucocytes not only confer analgesia but recent evidence supports the concept that they also prevent the development of tolerance at peripheral opioid receptors. This review presents the discoveries that led to the concept of analgesia produced by immune-derived opioids.
Topics: Analgesics, Opioid; Animals; Chemotaxis, Leukocyte; Drug Tolerance; Humans; Inflammation; Leukocytes; Opioid Peptides; Pain; Rats
PubMed: 18397920
DOI: 10.1093/bja/aen078 -
EMBO Molecular Medicine Aug 2017Myeloid leucocytes mediate host protection against infection and critically regulate inflammatory responses in body tissues. Pattern recognition receptor signalling is... (Review)
Review
Myeloid leucocytes mediate host protection against infection and critically regulate inflammatory responses in body tissues. Pattern recognition receptor signalling is crucial for myeloid cell responses to pathogens, but growing evidence suggests an equally potent role for Calcineurin-NFAT signalling in control of myeloid cell function. All major subsets of myeloid leucocytes employ Calcineurin-NFAT signalling during immune responses to pathogens and/or tissue damage, but the influence this pathway exerts on pathogen clearance and host susceptibility to infection is not fully understood. Recent data from experimental models indicate that Calcineurin-NFAT signalling is essential for infection control, and calcineurin inhibitors used in transplantation medicine (including cyclosporine A and tacrolimus) are now being tested for efficacy in a diverse range of inflammatory conditions and autoimmune pathologies. Efforts to repurpose calcineurin inhibitor drugs for new therapeutic applications may yield rapid improvements in clinical outcomes, but the potential impact of these compounds on myeloid cell function in treated patients is largely unknown. Here we discuss Calcineurin-NFAT control of myeloid leucocyte function in the context of recent therapeutic developments and ongoing clinical studies.
Topics: Calcineurin; Humans; Immunosuppressive Agents; Leukocytes; NFATC Transcription Factors; Signal Transduction
PubMed: 28606994
DOI: 10.15252/emmm.201707698