scholarly journals Biological Response Modifier Activity of an Exopolysaccharide from Paenibacillus jamilae CP-7

2001 ◽  
Vol 8 (4) ◽  
pp. 706-710 ◽  
Author(s):  
Alfonso Ruiz-Bravo ◽  
Maria Jimenez-Valera ◽  
Encarnacion Moreno ◽  
Victor Guerra ◽  
Alberto Ramos-Cormenzana

ABSTRACT An extracellular polysaccharide was purified from culture supernatants of Paenibacillus jamilae CP-7, a gram-positive bacillus that was isolated from compost prepared with olive mill wastewaters. The extracellular polysaccharide was produced under aerobic conditions in a medium containing olive mill wastewaters (80% [vol/vol]). This exopolymer had a low level of acute toxicity when it is administered to BALB/c mice by the intraperitoneal route. Interesting immunomodulatory effects were detected when mice were given 10 mg of exopolysaccharide per kg of body weight; the proliferative responses of splenocytes to B-cell and T-cell mitogens were suppressed, the in vitro levels of production of gamma interferon and granulocyte-macrophage colony-stimulating factor by unstimulated and lipopolysaccharide-stimulated splenocytes were enhanced, and the levels of resistance to the intracellular pathogen Listeria monocytogenes was increased in mice. Also, the exopolysaccharide was able to induce lymphocyte proliferation in vitro. We conclude thatP. jamilae produces an exopolysaccharide with interesting immunomodulatory properties.

Blood ◽  
1988 ◽  
Vol 72 (4) ◽  
pp. 1340-1347
Author(s):  
J Cebon ◽  
P Dempsey ◽  
R Fox ◽  
G Kannourakis ◽  
E Bonnem ◽  
...  

A sensitive and reliable sandwich enzyme-linked immunosorbent assay (ELISA) has been developed for recombinant human granulocyte-macrophage colony-stimulating factor (hGM-CSF). The assay is quantitative between 100 pg/mL and 2.5 ng/mL for bacterially synthesized hGM-CSF in human serum and is more sensitive and specific than the semisolid agar bioassay. As part of a phase I study, the pharmacokinetics of intravenous (IV) bolus injection and subcutaneous (SC) administration of hGM-CSF were studied. Following a single IV dose, an initial high blood level of hGM-CSF occurred, followed by a rapid decrease occurring in two apparent phases with a half-life (t1/2)alpha of less than five minutes and a t1/2 beta of 150 minutes. After an SC injection, detectable serum levels occurred within 15 to 30 minutes, and serum levels were sustained for a variable time depending on the dose. At the highest SC dose (10 micrograms/kg), a serum level of greater than 1 ng/mL (65 pmol/L) was maintained for greater than 12 hours after a single injection. This corresponds to the concentration of hGM-CSF supporting near-maximum proliferation in vitro.


Blood ◽  
1988 ◽  
Vol 72 (4) ◽  
pp. 1340-1347 ◽  
Author(s):  
J Cebon ◽  
P Dempsey ◽  
R Fox ◽  
G Kannourakis ◽  
E Bonnem ◽  
...  

Abstract A sensitive and reliable sandwich enzyme-linked immunosorbent assay (ELISA) has been developed for recombinant human granulocyte-macrophage colony-stimulating factor (hGM-CSF). The assay is quantitative between 100 pg/mL and 2.5 ng/mL for bacterially synthesized hGM-CSF in human serum and is more sensitive and specific than the semisolid agar bioassay. As part of a phase I study, the pharmacokinetics of intravenous (IV) bolus injection and subcutaneous (SC) administration of hGM-CSF were studied. Following a single IV dose, an initial high blood level of hGM-CSF occurred, followed by a rapid decrease occurring in two apparent phases with a half-life (t1/2)alpha of less than five minutes and a t1/2 beta of 150 minutes. After an SC injection, detectable serum levels occurred within 15 to 30 minutes, and serum levels were sustained for a variable time depending on the dose. At the highest SC dose (10 micrograms/kg), a serum level of greater than 1 ng/mL (65 pmol/L) was maintained for greater than 12 hours after a single injection. This corresponds to the concentration of hGM-CSF supporting near-maximum proliferation in vitro.


2000 ◽  
Vol 204 (2) ◽  
pp. 114-127 ◽  
Author(s):  
Roberto P. Revoltella ◽  
Leopoldo Laricchia Robbio ◽  
Anna Marina Liberati ◽  
Gigliola Reato ◽  
Robin Foa ◽  
...  

Blood ◽  
2018 ◽  
Vol 132 (17) ◽  
pp. 1818-1828 ◽  
Author(s):  
Laurel E. Hind ◽  
Patrick N. Ingram ◽  
David J. Beebe ◽  
Anna Huttenlocher

Abstract Neutrophil infiltration into tissues is essential for host defense and pathogen clearance. Although many of the signaling pathways involved in the transendothelial migration of neutrophils are known, the role of the endothelium in regulating neutrophil behavior in response to infection within interstitial tissues remains unclear. Here we developed a microscale 3-dimensional (3D) model that incorporates an endothelial lumen, a 3D extracellular matrix, and an intact bacterial source to model the host microenvironment. Using this system, we show that an endothelial lumen significantly increased neutrophil migration toward a source of Pseudomonas aeruginosa. Surprisingly, we found neutrophils, which were thought to be short-lived cells in vitro, migrate for up to 24 hours in 3D in the presence of an endothelial lumen and bacteria. In addition, we found that endothelial cells secrete inflammatory mediators induced by the presence of P aeruginosa, including granulocyte-macrophage colony-stimulating factor (GM-CSF), a known promoter of neutrophil survival, and interleukin (IL)-6, a proinflammatory cytokine. We found that pretreatment of neutrophils with a blocking antibody against the IL-6 receptor significantly reduced neutrophil migration to P aeruginosa but did not alter neutrophil lifetime, indicating that secreted IL-6 is an important signal between endothelial cells and neutrophils that mediates migration. Taken together, these findings demonstrate an important role for endothelial paracrine signaling in neutrophil migration and survival.


Blood ◽  
1988 ◽  
Vol 72 (3) ◽  
pp. 1077-1080 ◽  
Author(s):  
JJ Jimenez ◽  
AA Yunis

We have previously demonstrated that cultured rat chloroleukemia cells, MIA C51, will terminally differentiate to macrophages when treated with rat lung-conditioned medium in vitro and in vivo. In the present study we fractionated rat monocyte-conditioned medium by ultrafiltration according to molecular size. The fraction with molecular weight (mol wt) 30 to 50 Kd containing partially purified granulocyte-macrophage colony-stimulating factor (GM-CSF) activity caused the differentiation of C51 cells to macrophages in vitro and in diffusion chambers in vivo. Treatment of young rats with this fraction aborted the development of chloroleukemia from transplanted C51 cells. In contrast, the fraction with mol wt 10 to 30 Kd containing virtually all the G-CSF activity exhibited no differentiation activity either in vitro or in vivo. It is concluded that in this rat myelogenous leukemia model partially purified GM-CSF but not G-CSF contains the effector molecule(s) causing terminal differentiation of C51 cells and tumor cell rejection.


Blood ◽  
1988 ◽  
Vol 72 (4) ◽  
pp. 1329-1332 ◽  
Author(s):  
DC Kaufman ◽  
MR Baer ◽  
XZ Gao ◽  
ZQ Wang ◽  
HD Preisler

Expression of the granulocyte-macrophage colony-stimulating factor (GM- CSF) gene in acute myelocytic leukemia (AML) was assayed by Northern blot analysis. GM-CSF messenger RNA (mRNA) was detected in the freshly obtained mononuclear cells of only one of 48 cases of AML, in contrast with recent reports that GM-CSF mRNA might be detected in half of the cases of AML when RNA is prepared from T-cell- and monocyte-depleted leukemic cells. We did find, however, that expression of the GM-CSF gene was detectable in five of ten cases after in vitro T-cell and monocyte depletion steps. Additional studies suggest that expression of GM-CSF in the bone marrow of the one positive case, rather than being autonomous, was under exogenous control, possibly by a paracrine factor secreted by marrow stromal cells. These studies emphasize the potential for altering in vivo patterns of gene expression by in vitro cell manipulation.


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