scholarly journals Basophils, a neglected minority in the immune system, have come into the limelight at last

2021 ◽  
Author(s):  
Hajime Karasuyama ◽  
Sho Shibata ◽  
Soichiro Yoshikawa ◽  
Kensuke Miyake
Keyword(s):  
Mast Cells ◽  
Protective Immunity ◽  
Animal Studies ◽  
Genetically Engineered ◽  
Parasitic Infections ◽  
Genetically Engineered Mice ◽  
Analytical Tools ◽  
Human Basophils ◽  
Paul Ehrlich ◽  
New Strategies

Abstract Basophils, the rarest granulocytes, were identified by Paul Ehrlich more than 140 years ago, much earlier than the discovery of T and B cells. Unfortunately, basophils were often mixed up with tissue-resident mast cells because of some phenotypic similarities between them and considered erroneously as minor relatives or blood-circulating precursors of mast cells. Moreover, basophil research was hindered by the rarity of basophils and the paucity of useful analytical tools, and therefore basophils had often been neglected in immunological studies. A series of studies using newly developed tools, including basophil-depleting antibodies and genetically engineered mice deficient only in basophils, have clearly defined previously unrecognized roles of basophils, that are distinct from those played by tissue-resident mast cells. In this mini-review, we highlight recent advances in our understanding of basophil functions, particularly focusing on their roles in the regulation of innate and acquired immunity, allergic reactions, autoimmunity and protective immunity against parasitic infections, mainly based on animal studies. Further studies on human basophils would facilitate the development of new strategies for the treatment of basophil-associated disorders.

Lack of neurokinin-1 receptor expression affects tissue mast cell numbers but not their spatial relationship with nerves

2005 ◽  
Vol 288 (2) ◽  
pp. R491-R500 ◽  
Author(s):  
Michael R. D'Andrea ◽  
Marcia R. Saban ◽  
Norma P. Gerard ◽  
Barry K. Wershil ◽  
Ricardo Saban
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Spatial Association ◽  
Spatial Relationship ◽  
Genetically Engineered ◽  
Receptor Expression ◽  
Wild Type ◽  
Genetically Engineered Mice ◽  
Neurokinin 1 ◽  
Anatomic Relationship

A spatial association between mast cells and nerves has been described in both the gastrointestinal and genitourinary tracts. However, the factors that influence the anatomic relationship between mast cells and nerves have not been completely defined. It has been suggested that the high-affinity receptor for substance P [neurokinin-1 (NK1)] might modulate this interaction. We therefore assessed mast cell-nerve relationships in tissues isolated from wild-type and NK1 receptor knockout (NK1−/−) mice. We now report that, in the complete absence of NK1 receptor expression, there is a significant increase in the number of mast cells without a change in the anatomic relationship between mast cell and nerves in stomach and bladder tissues at the light microscopic level. We next determined whether transplanted mast cells would maintain their spatial distribution, number, and contact with nerve elements. For this purpose, mast cell-deficient Kit W /Kit W−v mice were reconstituted with wild-type or NK1−/− bone marrow. No differences in mast cell-nerve contact were observed. These results suggest that NK1 receptor expression is important in the regulation of the number of mast cells but is not important in the interaction between mast cells and nerves. Furthermore, the interaction between mast cells and nerves is not mediated through NK1 receptor expression on the mast cell. Further studies are needed to determine the molecular pathway involved in mast cell migration and interaction with nerve elements, but the model of reconstitution of Kit W /Kit W−v mice with mast cells derived from different genetically engineered mice is a useful approach to further explore these mechanisms.

Mast Cells and Tumor Progression.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. SCI-33-SCI-33
Author(s):  
D. Wade Clapp ◽  
Fengchun Yang ◽  
David A. Ingram ◽  
Kent A. Robertson ◽  
Gary D. Hutchins ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cells ◽  
Schwann Cell ◽  
Tumor Progression ◽  
Schwann Cells ◽  
Plexiform Neurofibroma ◽  
Genetically Engineered ◽  
Cell Functions ◽  
Kit Ligand ◽  
Genetically Engineered Mice

Abstract Abstract SCI-33 Interactions between tumorigenic cells and their surrounding microenvironment are critical for tumor progression yet remain incompletely understood. Germline mutations in the NF1 tumor suppressor gene cause neurofibromatosis type 1 (NF1), a common genetic disorder characterized by complex tumors called neurofibromas. Neurofibromas form in association with peripheral nerves and are composed of Schwann cells, blood vessels, fibroblasts and degranulating mast cells. Genetic studies in engineered mice indicate that biallelic loss of Nf1 is required in the tumorigenic cell of origin in the embryonic Schwann cell lineage. However, in the physiologic state, Schwann cell loss of heterozygosity is not sufficient for neurofibroma formation in a genetically engineered murine model and Nf1 haploinsufficiency in at least one additional nonneoplastic lineage is required for tumor progression. Recent studies in our group have focused on evaluating the role of bone marrow-derived cells, and particularly mast cells, in the tumor microenvironment. Previous work by our group established that human and murine Nf1 deficient Schwann cells secrete high concentrations of kit-ligand. Kit-ligand has a central role in multiple mast cell functions including chemotaxis, proliferation and degranulation. In a series of bone marrow transplantation studies, we established that Nf1 haploinsufficiency in bone marrow is sufficient to allow neurofibroma progression in the context of Schwann cell Nf1 deficiency. Further, genetic or pharmacologic attenuation of c-kit signaling diminishes neurofibroma initiation and progression. Collectively, the studies implicate mast cells as active participants in tumor formation and identify therapeutic targets for human phase 1-2 clinical trials. Disclosures Off Label Use: The drug imatinib mesylate was used to treat plexiform neurofibromas in genetically engineered mice, in a child with a plexiform neurofibroma, and it is currently being tested in a phase 2 clinical trial.

scholarly journals Toxicity modelling of Plk1-targeted therapies in genetically engineered mice and cultured primary mammalian cells

2011 ◽  
Vol 2 (1) ◽  
Author(s):  
Monika Raab ◽  
Sven Kappel ◽  
Andrea Krämer ◽  
Mourad Sanhaji ◽  
Yves Matthess ◽  
...  
Keyword(s):  
Targeted Therapies ◽  
Mammalian Cells ◽  
Genetically Engineered ◽  
Genetically Engineered Mice

scholarly journals Tenascin-C in Heart Diseases—The Role of Inflammation

2021 ◽  
Vol 22 (11) ◽  
pp. 5828
Author(s):  
Kyoko Imanaka-Yoshida
Keyword(s):  
Ventricular Remodeling ◽  
Heart Diseases ◽  
Genetically Engineered ◽  
Matricellular Protein ◽  
Myocardial Repair ◽  
Inflammatory Reactions ◽  
Tenascin C ◽  
Genetically Engineered Mice

Tenascin-C (TNC) is a large extracellular matrix (ECM) glycoprotein and an original member of the matricellular protein family. TNC is transiently expressed in the heart during embryonic development, but is rarely detected in normal adults; however, its expression is strongly up-regulated with inflammation. Although neither TNC-knockout nor -overexpressing mice show a distinct phenotype, disease models using genetically engineered mice combined with in vitro experiments have revealed multiple significant roles for TNC in responses to injury and myocardial repair, particularly in the regulation of inflammation. In most cases, TNC appears to deteriorate adverse ventricular remodeling by aggravating inflammation/fibrosis. Furthermore, accumulating clinical evidence has shown that high TNC levels predict adverse ventricular remodeling and a poor prognosis in patients with various heart diseases. Since the importance of inflammation has attracted attention in the pathophysiology of heart diseases, this review will focus on the roles of TNC in various types of inflammatory reactions, such as myocardial infarction, hypertensive fibrosis, myocarditis caused by viral infection or autoimmunity, and dilated cardiomyopathy. The utility of TNC as a biomarker for the stratification of myocardial disease conditions and the selection of appropriate therapies will also be discussed from a clinical viewpoint.

scholarly journals Characterization and visualization of murine coagulation factor VIII-producing cells in vivo

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Morisada Hayakawa ◽  
Asuka Sakata ◽  
Hiroko Hayakawa ◽  
Hikari Matsumoto ◽  
Takafumi Hiramoto ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Factor Viii ◽  
Fluorescent Protein ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Genetically Engineered ◽  
Coagulation Factor Viii ◽  
Liver Sinusoidal Endothelial Cells ◽  
Genetically Engineered Mice

AbstractCoagulation factors are produced from hepatocytes, whereas production of coagulation factor VIII (FVIII) from primary tissues and cell species is still controversial. Here, we tried to characterize primary FVIII-producing organ and cell species using genetically engineered mice, in which enhanced green fluorescent protein (EGFP) was expressed instead of the F8 gene. EGFP-positive FVIII-producing cells existed only in thin sinusoidal layer of the liver and characterized as CD31high, CD146high, and lymphatic vascular endothelial hyaluronan receptor 1 (Lyve1)+. EGFP-positive cells can be clearly distinguished from lymphatic endothelial cells in the expression profile of the podoplanin− and C-type lectin-like receptor-2 (CLEC-2)+. In embryogenesis, EGFP-positive cells began to emerge at E14.5 and subsequently increased according to liver maturation. Furthermore, plasma FVIII could be abolished by crossing F8 conditional deficient mice with Lyve1-Cre mice. In conclusion, in mice, FVIII is only produced from endothelial cells exhibiting CD31high, CD146high, Lyve1+, CLEC-2+, and podoplanin− in liver sinusoidal endothelial cells.

scholarly journals Ultrastructural Studies of Human Basophils and Mast Cells

2005 ◽  
Vol 53 (9) ◽  
pp. 1043-1070 ◽  
Author(s):  
Ann M. Dvorak
Keyword(s):  
Growth Factor ◽  
Mast Cells ◽  
Cord Blood ◽  
Blood Cells ◽  
De Novo ◽  
Ultrastructural Studies ◽  
Specific Growth Factor ◽  
Cord Blood Cells ◽  
Human Basophils

Ultrastructural studies of human mast cells (HMCs) and basophils (HBs) are reviewed. Sources of HMCs include biopsies of tissue sites and in situ study of excised diseased organs; isolated, partially purified samples from excised organs; and growth-factor-stimulated mast cells that develop de novo in cultures of cord blood cells. Sources of HBs for study include partially purified peripheral blood basophils, basophils in tissue biopsies, and specific growth factor-stimulated basophils arising de novo from cord blood cells. The ultrastructural studies reviewed deal with identity, secretion, vesicles, recovery, and synthesis issues related to the biology of these similar cells.

scholarly journals Immune Competency of a Hairless Mouse Strain for Improved Preclinical Studies in Genetically Engineered Mice

2010 ◽  
Vol 9 (8) ◽  
pp. 2354-2364 ◽  
Author(s):  
Beverly S. Schaffer ◽  
Marcia H. Grayson ◽  
Joy M. Wortham ◽  
Courtney B. Kubicek ◽  
Amanda T. McCleish ◽  
...  
Keyword(s):  
Mouse Strain ◽  
Hairless Mouse ◽  
Genetically Engineered ◽  
Preclinical Studies ◽  
Genetically Engineered Mice ◽  
Immune Competency

scholarly journals miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice

2011 ◽  
Vol 208 (6) ◽  
pp. 1189-1201 ◽  
Author(s):  
Mark P. Boldin ◽  
Konstantin D. Taganov ◽  
Dinesh S. Rao ◽  
Lili Yang ◽  
Jimmy L. Zhao ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Immune Cell ◽  
Myeloid Cell ◽  
Genetically Engineered ◽  
Biological Processes ◽  
Targeted Deletion ◽  
Genetically Engineered Mice ◽  
Immune Defects ◽  
Molecular Brake

Excessive or inappropriate activation of the immune system can be deleterious to the organism, warranting multiple molecular mechanisms to control and properly terminate immune responses. MicroRNAs (miRNAs), ∼22-nt-long noncoding RNAs, have recently emerged as key posttranscriptional regulators, controlling diverse biological processes, including responses to non-self. In this study, we examine the biological role of miR-146a using genetically engineered mice and show that targeted deletion of this gene, whose expression is strongly up-regulated after immune cell maturation and/or activation, results in several immune defects. Collectively, our findings suggest that miR-146a plays a key role as a molecular brake on inflammation, myeloid cell proliferation, and oncogenic transformation.

Sign in / Sign up

Export Citation Format

Share Document