scholarly journals Isolation, Synthesis, and Antimicrobial Activities of Naturally Occurring θ-Defensin Isoforms from Baboon Leukocytes

2008 ◽  
Vol 76 (12) ◽  
pp. 5883-5891 ◽  
Author(s):  
Angie E. Garcia ◽  
George Ösapay ◽  
Patti A. Tran ◽  
Jun Yuan ◽  
Michael E. Selsted
Keyword(s):  
Bone Marrow ◽  
Single Species ◽  
Antimicrobial Activities ◽  
Peripheral Blood Leukocytes ◽  
Blood Leukocytes ◽  
Naturally Occurring ◽  
Test Organisms ◽  
High Degree

ABSTRACT θ-Defensins are macrocyclic antimicrobial peptides that were previously isolated from leukocytes of a single species, the rhesus macaque. We now report the characterization of baboon θ-defensins (BTDs) expressed in bone marrow and peripheral blood leukocytes. Four cDNAs encoding θ-defensin precursors were characterized, allowing for the prediction of 10 theoretical θ-defensins (BTD-1 to BTD-10) produced by binary, head-to-tail splicing of nonapeptides excised from paired precursors. Five of the predicted θ-defensins were purified from baboon leukocytes, and synthetic versions of each were prepared. Anti-θ-defensin antibody localized the peptides in circulating neutrophils and monocytes and in immature and mature myeloid elements in bone marrow. Each of the BTDs possessed antimicrobial activity against bacterial and fungal test organisms in vitro. Peptide activities varied markedly despite a high degree of sequence conservation among the θ-defensins tested. Thus, baboons express numerous θ-defensins which appear to differentially contribute to host defense against diverse pathogens.

Functional and Biochemical Characterization of Immunologically Derived Equine Platelet-Activating Factor

1985 ◽  
Vol 22 (4) ◽  
pp. 375-386 ◽  
Author(s):  
H. C. Wimberly ◽  
D. O. Slauson ◽  
N. R. Neilsen
Keyword(s):  
Functional Activity ◽  
Biochemical Characterization ◽  
Platelet Activating Factor ◽  
Biochemical Properties ◽  
Naturally Occurring ◽  
Rabbit Platelets ◽  
Rapid Reaction ◽  
Specific Challenge

Antigen-specific challenge of equine leukocytes induced the non-lytic release of a platelet-activating factor in vitro. The equine platelet-activating factor stimulated the release of serotonin from equine platelets in a dose-responsive manner, independent of the presence of cyclo-oxygenase pathway inhibitors such as indomethacin. Rabbit platelets were also responsive to equine platelet-activating factor. The release of equine platelet-activating factor was a rapid reaction with near maximal secretion taking place in 30 seconds. Addition of equine platelet-activating factor to washed equine platelets stimulated platelet aggregation which could not be inhibited by the presence of aspirin or indomethacin. Platelets preincubated with equine platelet-activating factor became specifically desensitized to equine platelet-activating factor while remaining responsive to other platelet stimuli such as collagen and epinephrine. The following biochemical properties of equine platelet-activating factor are identical to those properties of 1-0-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (AGEPC): stability upon exposure to air and acid; loss of functional activity after basecatalyzed methanolysis with subsequent acylation that returned all functional activity; and identical relative mobilities on silica gel G plates developed with chloroform:methanol:water (65:35:6, volume/volume). The combined functional and biochemical characteristics of equine platelet-activating factor strongly suggest identity between this naturally occurring, immunologically derived equine factor and AGEPC.

scholarly journals Congenital neutropenia: neutrophil proliferation with abnormal maturation

Blood ◽  
1975 ◽  
Vol 46 (5) ◽  
pp. 723-734 ◽  
Author(s):  
RT Parmley ◽  
M Ogawa ◽  
CP Jr Darby ◽  
SS Spicer
Keyword(s):  
Bone Marrow ◽  
Acid Phosphatase ◽  
Colony Stimulating Factor ◽  
Peripheral Blood Leukocytes ◽  
Congenital Neutropenia ◽  
Blood Leukocytes ◽  
Specific Granules ◽  
Primary Granules ◽  
Stimulating Factor ◽  
Myelin Figures

Abstract A child with congenital neutropenia was studied using bone marrow culture and ultrastructural and cytochemical techniques. The patient's marrow cells formed a large number of granulocytic colonies of normal size in culture, and her peripheral blood leukocytes produced adequate colony-stimulating factor. No serum inhibitors were identified. The patient's promyelocytes from direct marrow and culture appeared normal in ultrastructure, and primary granules, contained peroxidase and acid phosphatase activity. Myelocytes and rare segmented neutrophils from direct marrow specimens demonstrated atypical notched nuclei, myelin figures in Golgi lamellae and primary (azurophilic) granules, and no identifiable secondary (specific) granules. These data indicate an intrinsic neutrophil defect which allows normal proliferation of precursor cells, but results in abnormal granulogenesis and apparent inability to form secondary granules.

scholarly journals Preclinical Evidence of Nanomedicine Formulation to Target Mycobacterium tuberculosis at Its Bone Marrow Niche

Pathogens ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 372 ◽  
Author(s):  
Jaishree Garhyan ◽  
Surender Mohan ◽  
Vinoth Rajendran ◽  
Rakesh Bhatnagar
Keyword(s):  
Bone Marrow ◽  
Mycobacterium Tuberculosis ◽  
In Vitro Release ◽  
Bone Marrow Niche ◽  
Mice Model ◽  
Latently Infected ◽  
Marrow Mesenchymal Stem Cells

One-third of the world’s population is estimated to be latently infected with Mycobacterium tuberculosis (Mtb). Recently, we found that dormant Mtb hides in bone marrow mesenchymal stem cells (BM-MSCs) post-chemotherapy in mice model and in clinical subjects. It is known that residual Mtb post-chemotherapy may be responsible for increased relapse rates. However, strategies for Mtb clearance post-chemotherapy are lacking. In this study, we engineered and formulated novel bone-homing PEGylated liposome nanoparticles (BTL-NPs) which actively targeted the bone microenvironment leading to Mtb clearance. Targeting of BM-resident Mtb was carried out through bone-homing liposomes tagged with alendronate (Ald). BTL characterization using TEM and DLS showed that the size of bone-homing isoniazid (INH) and rifampicin (RIF) BTLs were 100 ± 16.3 nm and 84 ± 18.4 nm, respectively, with the encapsulation efficiency of 69.5% ± 4.2% and 70.6% ± 4.7%. Further characterization of BTLs, displayed by sustained in vitro release patterns, increased in vivo tissue uptake and enhanced internalization of BTLs in RAW cells and CD271+BM-MSCs. The efficacy of isoniazid (INH)- and rifampicin (RIF)-loaded BTLs were shown using a mice model where the relapse rate of the tuberculosis was decreased significantly in targeted versus non-targeted groups. Our findings suggest that BTLs may play an important role in developing a clinical strategy for the clearance of dormant Mtb post-chemotherapy in BM cells.

scholarly journals Isolation and characterization of adrenocortical progenitors involved in the adaptation to stress

2018 ◽  
Vol 115 (51) ◽  
pp. 12997-13002 ◽  
Author(s):  
Charlotte Steenblock ◽  
Maria F. Rubin de Celis ◽  
Luis F. Delgadillo Silva ◽  
Verena Pawolski ◽  
Ana Brennand ◽  
...  
Keyword(s):  
Lineage Tracing ◽  
Differentiated Cells ◽  
Isolation And Characterization ◽  
Proliferation And Differentiation ◽  
Response To Stress ◽  
Steroidogenic Cells ◽  
High Degree

The adrenal gland is a master regulator of the human body during response to stress. This organ shows constant replacement of senescent cells by newly differentiated cells. A high degree of plasticity is critical to sustain homeostasis under different physiological demands. This is achieved in part through proliferation and differentiation of adult adrenal progenitors. Here, we report the isolation and characterization of a Nestin+ population of adrenocortical progenitors located under the adrenal capsule and scattered throughout the cortex. These cells are interconnected with progenitors in the medulla. In vivo lineage tracing revealed that, under basal conditions, this population is noncommitted and slowly migrates centripetally. Under stress, this migration is greatly enhanced, and the cells differentiate into steroidogenic cells. Nestin+ cells cultured in vitro also show multipotency, as they differentiate into mineralocorticoid and glucocorticoid-producing cells, which can be further influenced by the exposure to Angiotensin II, adrenocorticotropic hormone, and the agonist of luteinizing hormone-releasing hormone, triptorelin. Taken together, Nestin+ cells in the adult adrenal cortex exhibit the features of adrenocortical progenitor cells. Our study provides evidence for a role of Nestin+ cells in organ homeostasis and emphasizes their role under stress. This cell population might be a potential source of cell replacement for the treatment of adrenal insufficiency.

scholarly journals Evaluation of antigenotoxic potential of salvianolic acid B with hydrogen peroxide on human peripheral blood leukocytes in vitro

2017 ◽  
Vol 51 (2) ◽  
pp. 39-45
Author(s):  
Milena Jankovic ◽  
Lada Zivkovic ◽  
Andrea Pirkovic ◽  
Dijana Topalovic ◽  
Dragana Dekanski ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Salvianolic Acid B ◽  
Peripheral Blood Leukocytes ◽  
Blood Leukocytes ◽  
Salvianolic Acid

scholarly journals Immune reactions in human filariasis

1978 ◽  
Vol 8 (2) ◽  
pp. 228-232 ◽  
Author(s):  
D Subrahmanyam ◽  
K Mehta ◽  
D S Nelson ◽  
Y V Rao ◽  
C K Rao
Keyword(s):  
Immunoglobulin G ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Wuchereria Bancrofti ◽  
Normal Subjects ◽  
Peripheral Blood Leukocytes ◽  
51Cr Release ◽  
Blood Leukocytes ◽  
Release Studies

Sera from cases of elephantiasis due to Wuchereria bancrofti infection promoted an intense adhesion of peripheral blood leukocytes to W. bancrofti microfilariae in vitro. A similar adhesion was also seen using sera from some normal persons living for several years in areas where filariasis is endemic. No such adhesion was evident with sera from microfilaria carriers or from normal subjects from nonendemic areas. The adhesion was complement independent and was associated with the immunoglobulin G fraction of serum. 51Cr release studies suggested the occurrence of cell-mediated cytotoxicity to W. bancrofti microfilariae in the presence of elephantiasis serum. Microfilariae of Litomosoides carinii could be isolated free of blood cells, from the blood of infected rats. In the presence of serum, or its immunoglobulin G fraction, from patients with elephantiasis, L. carinii microfilariae adhered to human peripheral blood leukocytes or rat spleen cells.

scholarly journals Induction of superoxide dismutase in leukocytes by paraquat: correlation with age and possible predictor of longevity

Blood ◽  
1990 ◽  
Vol 76 (4) ◽  
pp. 835-841 ◽  
Author(s):  
Y Niwa ◽  
K Ishimoto ◽  
T Kanoh
Keyword(s):  
Superoxide Dismutase ◽  
Healthy Subjects ◽  
Oxygen Species ◽  
Peripheral Blood Leukocytes ◽  
Blood Leukocytes ◽  
Sod Activity ◽  
Elderly Individuals ◽  
Age Dependent ◽  
O2 Production

Reactive oxygen species (ROS) are thought to play a role in the aging process as well as in a number of human diseases states. Superoxide dismutase (SOD), an enzyme that scavenges the superoxide anion (O2-) is constitutively expressed in leukocytes and other tissues. When assayed in peripheral blood leukocytes (PBL), constitutive SOD activity shows little variation among individuals of different ages. We have found that significant induction of SOD activity occurs in PBL incubated in vitro with paraquat, an agent known to cause intracellular O2- production. This induction was found to be highly age dependent; lymphocytes from 36 healthy subjects aged 20 to 40 years showed an increase of 85% +/- 10%, versus an increase of only 8% +/- 1% for lymphocytes from 30 healthy subjects aged 65 to 79 years (P less than 10(-4)). Forty subjects, aged 67 to 73 years, who were healthy at the time of assay of leukocyte SOD induction were followed up 5 years later. Nineteen of these subjects had died; all 19 had shown SOD induction of less than 10% (range, 0% to 7%; mean, 2.4%). In contrast, of the 21 survivors (range, 2.5% to 50%; mean, 21%), 12 had shown SOD induction greater than 10%, and 7 had shown SOD induction greater than or equal to 35% (P less than 10(-3)). Thirteen of the 19 deaths were attributable to malignancy or cerebrocardiovascular disease. Preservation of leukocyte SOD inducibility appears to correlate with longevity in elderly individuals and may be of value in predicting resistance to malignancy or fetal cardiovascular events.

scholarly journals Identification and characterization of RNA aptamers: A long aptamer blocks the AMPA receptor and a short aptamer blocks both AMPA and kainate receptors

2017 ◽  
Vol 292 (18) ◽  
pp. 7338-7347 ◽  
Author(s):  
William J. Jaremko ◽  
Zhen Huang ◽  
Wei Wen ◽  
Andrew Wu ◽  
Nicholas Karl ◽  
...  
Keyword(s):  
Ampa Receptor ◽  
Neurological Diseases ◽  
Rna Aptamers ◽  
Kainate Receptors ◽  
Single Receptor ◽  
Cell Recording ◽  
Exponential Enrichment ◽  
High Degree

AMPA and kainate receptors, along with NMDA receptors, represent different subtypes of glutamate ion channels. AMPA and kainate receptors share a high degree of sequence and structural similarities, and excessive activity of these receptors has been implicated in neurological diseases such as epilepsy. Therefore, blocking detrimental activity of both receptor types could be therapeutically beneficial. Here, we report the use of an in vitro evolution approach involving systematic evolution of ligands by exponential enrichment with a single AMPA receptor target (i.e. GluA1/2R) to isolate RNA aptamers that can potentially inhibit both AMPA and kainate receptors. A full-length or 101-nucleotide (nt) aptamer selectively inhibited GluA1/2R with a KI of ∼5 μm, along with GluA1 and GluA2 AMPA receptor subunits. Of note, its shorter version (55 nt) inhibited both AMPA and kainate receptors. In particular, this shorter aptamer blocked equally potently the activity of both the GluK1 and GluK2 kainate receptors. Using homologous binding and whole-cell recording assays, we found that an RNA aptamer most likely binds to the receptor's regulatory site and inhibits it noncompetitively. Our results suggest the potential of using a single receptor target to develop RNA aptamers with dual activity for effectively blocking both AMPA and kainate receptors.

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