scholarly journals IN VITRO AND IN VIVO ACTIVITY OF A LYMPHOCYTE AND IMMUNE COMPLEX-DEPENDENT CHEMOTACTIC FACTOR FOR EOSINOPHILS

1971 ◽  
Vol 133 (1) ◽  
pp. 133-146 ◽  
Author(s):  
Stanley Cohen ◽  
Peter A. Ward
Keyword(s):  
Immune Complexes ◽  
Specific Antigen ◽  
Biological Significance ◽  
Cell Types ◽  
Lymphocyte Culture ◽  
Chemotactic Factor ◽  
Biologically Active ◽  
Chemotactic Factors

When cultured in the presence of specific antigen, lymphocytes from delayed-hypersensitive guinea pigs release a number of biologically active substances into the culture medium. Such active supernatants can react with immune complexes in vitro to generate a factor which is chemotactic for eosinophils. The factor involved is unique, since previously described chemotactic factors for other cell types require for their generation either immune complexes or substances released into lymphocyte culture, but not both. In the case of the eosinophil chemotactic factor, the interaction between the substance elaborated by the lymphocytes and the immune complexes appears to be specific in that the immune complexes must contain the same antigen as that used to activate the lymphocyte cultures. Although this factor was generated in an in vitro system, it has been shown to possess in vivo as well as in vitro activity. It is therefore possible that this factor may be of biological significance in situations where eosinophils are participants in inflammatory or immunologic reactions.

scholarly journals FiloQuant reveals increased filopodia density during DCIS progression

2017 ◽  
Author(s):  
Guillaume Jacquemet ◽  
Ilkka Paatero ◽  
Alexandre F. Carisey ◽  
Artur Padzik ◽  
Jordan S. Orange ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Ductal Carcinoma ◽  
Biological Significance ◽  
Cell Types ◽  
Neuronal Cultures ◽  
Cellular Models ◽  
Tumour Spheroids ◽  
Microscopy Data

AbstractFilopodia are commonly observed cellular protrusions in vitro and in vivo. Defective filopodia formation is linked to several pathologies including cancer, wherein actively protruding filopodia, at the invasive front, and filopodia-mediated probing of the microenvironment accompanies cancer cell dissemination. Despite wide biological significance, delineating the function of these finger-like protrusions in more complex systems remains technically challenging, particularly hindered by lack of compatible methods to quantify filopodia properties. Here, we present FiloQuant, a freely available ImageJ plugin, to detect filopodia and filopodia-like protrusions in both fixed and live-cell microscopy data. We demonstrate that FiloQuant can extract quantifiable information including protrusion dynamics, density and length from multiple cell types and in a range of microenvironments, such as during collective or single cancer cell migration in 2D and 3D, in fixed neuronal cultures, in activated natural killer cells and in sprouting endothelial cells in vivo. In cellular models of breast ductal carcinoma in situ (DCIS) we reveal a link between filopodia formation at the cell-matrix interface, during collective invasion and in 3D tumour spheroids, with the previously reported local invasive potential of these breast cancer models in vivo. Finally, using intravital microscopy, we observed that tumour spheroids display prominent filopodia in vivo, supporting a potential role for these protrusions during tumorigenesis.

scholarly journals IGF-binding protein-4: biochemical characteristics and functional consequences

2003 ◽  
Vol 178 (2) ◽  
pp. 177-193 ◽  
Author(s):  
R Zhou ◽  
D Diehl ◽  
A Hoeflich ◽  
H Lahm ◽  
E Wolf
Keyword(s):  
Biological Fluids ◽  
Biological Significance ◽  
Structural Similarity ◽  
Cell Types ◽  
Cellular Growth ◽  
Igf Binding Proteins ◽  
Wide Range ◽  
Igf Binding

IGFs have multiple functions regarding cellular growth, survival and differentiation under different physiological and pathological conditions. IGF effects are modulated systemically and locally by six high-affinity IGF-binding proteins (IGFBP-1 to -6). Despite their structural similarity, each IGFBP has unique properties and exhibits specific functions. IGFBP-4, the smallest IGFBP, exists in both non-glycosylated and N-glycosylated forms in all biological fluids. It is expressed by a wide range of cell types and tIssues, and its expression is regulated by different mechanisms in a cell type-specific manner. IGFBP-4 binds IGF-I and IGF-II with similar affinities and inhibits their actions under almost all in vitro and in vivo conditions. In this review, we summarize the available data regarding the following aspects of IGFBP-4: genomic organization, protein structure-function relationship, expression and its regulation, as well as IGF-dependent and -independent actions. The biological significance of IGFBP-4 for reproductive physiology, bone formation, renal pathophysiology and cancer is discussed.

Phenotypic and functional analyses of dendritic cells in patients with lymphoproliferative disease of granular lymphocytes (LDGL)

Blood ◽  
2005 ◽  
Vol 106 (12) ◽  
pp. 3926-3931 ◽  
Author(s):  
Renato Zambello ◽  
Tamara Berno ◽  
Giovanna Cannas ◽  
Ilenia Baesso ◽  
Gianni Binotto ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Specific Antigen ◽  
Cell Types ◽  
Lymphoproliferative Disease ◽  
Topographic Organization ◽  
Functional Analyses ◽  
Granular Lymphocytes

We investigated whether dendritic cells (DCs) play a role in favoring granular lymphocyte (GL) proliferation in patients with lymphoproliferative disease of granular lymphocytes (LDGL). The presence of in vivo circulating DCs was studied in 11 patients (5 CD3+ and 6 CD3- LDGL). Autologous immature (iDCs) and mature (mDCs) DCs generated in vitro were studied for stimulatory activity on cell proliferation of CD3+ and CD3- GLs. The topographic organization of GLs and DCs was also studied in bone marrow (BM) biopsies. Peripheral blood (PB) CD3- GLs from patients showed significant proliferative activity in the presence of iDCs and mDCs. Conversely, monoclonal CD3+ GLs were unresponsive to autologous and allogeneic PB DCs. Analysis of BM biopsies demonstrated a topographic distribution of DCs and GLs that indicates contact between the 2 cell types. On functional assays, DCs obtained from BM were more efficient than PB DCs in stimulating CD3- GLs, and surprisingly, a low but definite stimulatory effect was demonstrated also on CD3+ GLs. The putative contact between DCs and GLs in the BM and, more crucial, the proliferative response of discrete GL populations to DC stimulation suggest the presence of a specific antigen within BM DCs, providing evidence for a role of DCs in the pathogenesis of LDGL.

scholarly journals A Review of Biologically Active Natural Products from Mediterranean Wild Edible Plants: Benefits in the Treatment of Obesity and Its Related Disorders

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 649 ◽  
Author(s):  
Mariangela Marrelli ◽  
Giancarlo Statti ◽  
Filomena Conforti
Keyword(s):  
Natural Products ◽  
Therapeutic Potential ◽  
Biological Significance ◽  
Biologically Active ◽  
Wild Food ◽  
Wild Foods ◽  
Food And Agriculture ◽  
Edible Species

Wild foods constitute an essential component of people’s diets around the world. According to the Food and Agriculture Organization (FAO), over 100 million people in the EU consume wild foods, while 65 million collect some form of wild food themselves. The Mediterranean basin is a biodiversity hotspot of wild edible species. Nowadays, due to the renewed interest in alimurgic plants and the recent findings on the beneficial role of their phytochemical constituents, these species have been defined as “new functional foods”. Research on natural products has recently regained importance with the growing understanding of their biological significance. Botanical food supplements marketed for weight and fat loss in obese subjects will be one of the most important items in marketed nutraceuticals. The aim of this report was to review the phytochemical compounds of Mediterranean wild edible species and their therapeutic potential against obesity and its related disorders. Results on the in vitro and in vivo activity of the most interesting plant extracts and their bioactive components are presented and discussed. The most interesting discoveries on their mechanisms of action are reported as well. Overall, this contribution highlights the importance and beneficial health roles of wild edible species.

scholarly journals Selective neutrophil desensitization to chemotactic factors.

1979 ◽  
Vol 80 (3) ◽  
pp. 564-572 ◽  
Author(s):  
J T O'Flaherty ◽  
D L Kreutzer ◽  
H J Showell ◽  
G Vitkauskas ◽  
E L Becker ◽  
...  
Keyword(s):  
Cellular Response ◽  
Chemotactic Factor ◽  
Polymorphonuclear Neutrophils ◽  
Functional Loss ◽  
Aggregation Response ◽  
Bivalent Cations ◽  
Chemotactic Factors ◽  
Calcium And Magnesium

In the presence of extracellular calcium and magnesium, a series of chemotactic oligopeptides and C5a caused aggregation of human polymorphonuclear neutrophils (PMNs). This cellular response developed rapidly and began to reverse 2 min after exposure to the chemotactin. In the absence of the bivalent cations, none of the chemotactins stimulated the aggregation response. If cells were first exposed to a chemotactin and then treated with calcium and magnesium, aggregation was detected only after addition of the cations, and the magnitude of the response fell sharply as the interval between the addition of chemotactin and addition of cations was lengthened: when this interval exceeded 2 min, aggregation was barely detectable. This loss of reactivity persisted even when cells were re-exposed to fresh chemotactic factor and washed between the first and second exposures. In all instances, however, loss of cellular reactivity was highly selective: cells preincubated with any chemotactic oligopeptide were hyporesponsive to subsequent stimulation with an oligopeptide but remained fully responsive to C5a; cells preincubated with C5A were hyporesponsive to C5a but retained their responsitivity to the oligopeptides. Because this selectivity parallels the known specificities of these chemotactic factors for their receptors in or on the neutrophil, desensitization may reflect functional loss of receptors after stimulation. Alternatively, this selectivity may indicate that morphologically identical neutrophils contain subpopulations of cells with varying reactivities to receptor-bound chemotactic factors. In either event, desensitization may be useful in functionally defining chemotactic factors and their respective receptors. The rapidity of development of desensitization suggests that it may operate to limit or moderate various in vitro and in vivo neutrophil responses to chemotactic factors.

scholarly journals Identification and Characterization of Mefloquine Efficacy against JC Virus In Vitro

2009 ◽  
Vol 53 (5) ◽  
pp. 1840-1849 ◽  
Author(s):  
Margot Brickelmaier ◽  
Alexey Lugovskoy ◽  
Ramya Kartikeyan ◽  
Marta M. Reviriego-Mendoza ◽  
Norm Allaire ◽  
...  
Keyword(s):  
Viral Entry ◽  
Cultured Cells ◽  
Jc Virus ◽  
Antiviral Treatment ◽  
Cell Types ◽  
Biologically Active ◽  
Biodistribution Data ◽  
Approved Drugs

ABSTRACT Progressive multifocal leukoencephalopathy (PML) is a rare but frequently fatal disease caused by the uncontrolled replication of JC virus (JCV), a polyomavirus, in the brains of some immunocompromised individuals. Currently, no effective antiviral treatment for this disease has been identified. As a first step in the identification of such therapy, we screened the Spectrum collection of 2,000 approved drugs and biologically active molecules for their anti-JCV activities in an in vitro infection assay. We identified a number of different drugs and compounds that had significant anti-JCV activities at micromolar concentrations and lacked cellular toxicity. Of the compounds with anti-JCV activities, only mefloquine, an antimalarial agent, has been reported to show sufficiently high penetration into the central nervous system such that it would be predicted to achieve efficacious concentrations in the brain. Additional in vitro experiments demonstrated that mefloquine inhibits the viral infection rates of three different JCV isolates, JCV(Mad1), JCV(Mad4), and JCV(M1/SVEΔ), and does so in three different cell types, transformed human glial (SVG-A) cells, primary human fetal glial cells, and primary human astrocytes. Using quantitative PCR to quantify the number of viral copies in cultured cells, we have also shown that mefloquine inhibits viral DNA replication. Finally, we demonstrated that mefloquine does not block viral cell entry; rather, it inhibits viral replication in cells after viral entry. Although no suitable animal model of PML or JCV infection is available for the testing of mefloquine in vivo, our in vitro results, combined with biodistribution data published in the literature, suggest that mefloquine could be an effective therapy for PML.

scholarly journals A PLASMIN-SPLIT FRAGMENT OF C'3 AS A NEW CHEMOTACTIC FACTOR

1967 ◽  
Vol 126 (2) ◽  
pp. 189-206 ◽  
Author(s):  
Peter A. Ward
Keyword(s):  
Sucrose Density Gradient ◽  
Chemotactic Factor ◽  
Biologically Active ◽  
Trimolecular Complex ◽  
Approximate Molecular Weight ◽  
Intact Molecule ◽  
Human Plasminogen ◽  
Active Fragments

When streptokinase and highly purified human plasminogen are added to human serum or to partly purified or highly purified preparations containing the third component of complement (C'3), either rabbit or human, a chemotactic factor is generated. This chemotactic factor is a split product of C'3 and is dialyzable, fast moving electrophoretically, slowly sedimenting in sucrose density gradient ultracentrifugation, and has an approximate molecular weight of 6000. It is calculated that this fragment accounts for approximately 4% of the intact molecule. The C'3 fragment has the following biologic properties: It is chemotactic for rabbit PMN's in vitro, it causes accumulation of PMN's in vivo, and it increases vascular permeability in rat skin. In addition to generating a chemotactic factor, plasmin destroys the complement-associated chemotactic factor that is a trimolecular complex consisting of the fifth (C'5), sixth (C'6), and seventh (C'7) components of complement. This has been shown by a loss of chemotactic activity, as well as a dissociation of the C'5, C'6, C'7 complex and a destruction of C'6 hemolytic activity. The biologic significance of the plasmin-generated chemotactic factor is discussed in relation to other recently discovered biologically active fragments of C'3.

Abstract 187: c-Kit Biology Revealed by Two Transgenic Reporter Models.

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Natalie A Gude ◽  
Fareheh Firouzi ◽  
Kristine Nguyen ◽  
Christina Payne ◽  
Veronica Sacchi ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Transgenic Mouse ◽  
Cardiac Myocyte ◽  
Biological Significance ◽  
Cell Types ◽  
Experimental Models ◽  
Model Systems ◽  
Transgenic Lines

Background: The biological significance of c-Kit as a marker of cardiac stem cells, and role(s) of c-Kit+ cells in myocardial development or in response to pathologic injury remain unresolved due to varied findings among investigators and experimental model systems. Alternative experimental models and approaches are needed to achieve a broader perspective of cardiac c-Kit biology that contextualizes discrepant published observations. Objectives: Tracking c-Kit expression using transgenesis overcomes limitations inherent to knock-in reporter models. Two novel, inducible transgenic c-Kit reporter models are presented in this study to further elaborate on myocardial c-Kit biology. Methods: A previously characterized mouse c-Kit promoter segment was engineered to generate a transgenic mouse in which rtTA transactivator is expressed in c-Kit+ cells (c-KitrtTA). c-KitrtTA crossed to Tet-Responsive-Element(TRE)-Histone2B-EGFP or TRE-Cre lines produces the CKH2B and CKCre double transgenic lines, which express doxycycline-inducible H2BEGFP or Cre proteins in c-Kit+ cells. The CKmTmG triple transgenic mouse, arising from CKCre crossed to the ROSAmTmG reporter line, utilizes doxycycline induced recombination to tag c-Kit+ cells irreversibly with membrane bound EGFP. Endogenous c-Kit and transgenic reporter expression was assessed in adult cardiac myocyte and nonmyocyte cells from these mice under resting and cellular stress conditions using immunohistochemistry and flow cytometry. Results: Coincidence of c-Kit and EGFP is observed in approximately 75% of freshly isolated nonmyocyte cells as detected by flow cytometry. A subpopulation of cardiomyocytes express H2BEGFP or mEGFP in the uninjured, doxycycline treated adult heart. H2BEGFP and c-Kit expression increase in myocytes in response to isoproterenol-induced pathologic stress in vivo and in vitro. Conclusion: These c-Kit transgenic reporter models provide sensitive, specific, inducible and persistent tracking of c-Kit promoter activation. Results presented here reveal an unexpected role for c-Kit expression in adult cardiomyocytes. Future studies will use both models to investigate c-Kit expression in all cell types during cardiac formation and repair.

scholarly journals FiloQuant reveals increased filopodia density during breast cancer progression

2017 ◽  
Vol 216 (10) ◽  
pp. 3387-3403 ◽  
Author(s):  
Guillaume Jacquemet ◽  
Ilkka Paatero ◽  
Alexandre F. Carisey ◽  
Artur Padzik ◽  
Jordan S. Orange ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Ductal Carcinoma ◽  
Biological Significance ◽  
Cell Types ◽  
Tumor Spheroids ◽  
Cellular Models ◽  
Invasive Capacity ◽  
Microscopy Data

Defective filopodia formation is linked to pathologies such as cancer, wherein actively protruding filopodia, at the invasive front, accompany cancer cell dissemination. Despite wide biological significance, delineating filopodia function in complex systems remains challenging and is particularly hindered by lack of compatible methods to quantify filopodia properties. Here, we present FiloQuant, a freely available ImageJ plugin, to detect filopodia-like protrusions in both fixed- and live-cell microscopy data. We demonstrate that FiloQuant can extract quantifiable information, including protrusion dynamics, density, and length, from multiple cell types and in a range of microenvironments. In cellular models of breast ductal carcinoma in situ, we reveal a link between filopodia formation at the cell–matrix interface, in collectively invading cells and 3D tumor spheroids, and the in vitro invasive capacity of the carcinoma. Finally, using intravital microscopy, we observe that tumor spheroids display filopodia in vivo, supporting a potential role for these protrusions during tumorigenesis.

Ultrastructural observations on the in vitro cytoadherence of Plasmodium falciparum infected red blood cells

1990 ◽  
Vol 48 (3) ◽  
pp. 914-915
Author(s):  
D.J.P. Ferguson ◽  
A.R. Berendt ◽  
J. Tansey ◽  
K. Marsh ◽  
C.I. Newbold
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Umbilical Vein ◽  
Cell Types ◽  
Amelanotic Melanoma ◽  
Cytoplasmic Process ◽  
Umbilical Vein Endothelial Cells

In human malaria, the most serious clinical manifestation is cerebral malaria (CM) due to infection with Plasmodium falciparum. The pathology of CM is thought to relate to the fact that red blood cells containing mature forms of the parasite (PRBC) cytoadhere or sequester to post capillary venules of various tissues including the brain. This in vivo phenomenon has been studied in vitro by examining the cytoadherence of PRBCs to various cell types and purified proteins. To date, three Ijiost receptor molecules have been identified; CD36, ICAM-1 and thrombospondin. The specific changes in the PRBC membrane which mediate cytoadherence are less well understood, but they include the sub-membranous deposition of electron-dense material resulting in surface deformations called knobs. Knobs were thought to be essential for cytoadherence, lput recent work has shown that certain knob-negative (K-) lines can cytoadhere. In the present study, we have used electron microscopy to re-examine the interactions between K+ PRBCs and both C32 amelanotic melanoma cells and human umbilical vein endothelial cells (HUVEC).We confirm previous data demonstrating that C32 cells possess numerous microvilli which adhere to the PRBC, mainly via the knobs (Fig. 1). In contrast, the HUVEC were relatively smooth and the PRBCs appeared partially flattened onto the cell surface (Fig. 2). Furthermore, many of the PRBCs exhibited an invagination of the limiting membrane in the attachment zone, often containing a cytoplasmic process from the endothelial cell (Fig. 2).

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