|
Beta Glucan
Radiation Research |
| Citation |
Abstract |
Patchen
ML, DiLuzio NR, Jacques P, MacVittie TJ.
Soluble polyglycans enhance
recovery from cobalt-60--induced hemopoietic
injury.
J Biol Response Mod. 1984 Dec;3(6):627-33.
PMID: 6512563 [PubMed - indexed for MEDLINE] |
Six
soluble polyglycans (glucan-C, glucan-F, glucan-S, krestin, lentinan, and
schizophyllan), two soluble polymannans (mannan-A
and mannan-R), and one soluble polyfructan
(levan) were assayed for their ability to enhance hemopoietic recovery in
C3H/HeN mice when administered either 1 h
before or 1 h after a 6.5-Gy dose of cobalt-60
radiation. Hemopoietic recovery was measured by the endogenous spleen colony assay and was compared with recovery in
both radiation control mice and irradiated
mice treated with glucan-P (a particulate polyglycan previously shown to enhance recovery from radiation-induced
hemopoietic injury). Compared with radiation controls,
when administered before irradiation, mannan-A, glucan-F, and glucan-S enhanced endogenous colony formation
4.2-5.1-fold (equivalent to glucan-P), and levan
and schizophyllan approximately 2.7-fold. Lentinan, krestin, mannan-R, and
glucan-C did not enhance hemopoietic recovery
above radiation controls under these conditions.
When polyglycan administration was delayed until after irradiation, endogenous colony formation was enhanced
3.0-3.9-fold by mannan-A, schizophyllan, glucan-S, krestin, and glucan-F (at least comparable with glucan-P) but not at all
by mannan-R, levan, lentinan, or
glucan-C. |
| Patchen
ML, MacVittie TJ, Wathen LM.
Effects of pre- and post-irradiation glucan treatment on
pluripotent stem cells, granulocyte, macrophage and erythroid progenitor
cells, and hemopoietic stromal cells.
Experientia. 1984 Nov 15;40(11): 1240-4.
PMID: 6500009 [PubMed - indexed for MEDLINE] |
Glucan,
a beta-1,3 polyglucose, was administered to mice either 1 h before or 1 h after a 650 rad exposure to cobalt-60
radiation. Compared to radiation controls, glucan-treated
mice consistently exhibited a more rapid recovery of pluripotent stem cells and committed granulocyte, macrophage,
and erythroid progenitor cells. This may
partially explain the mechanism by which glucan also enhances survival in otherwise lethally irradiated mice. |
| Patchen
ML, MacVittie TJ.
Stimulated hemopoiesis and enhanced survival following glucan
treatment in sublethally and lethally irradiated mice.
Int J Immunopharmacol. 1985;7(6): 923-32.
PMID: 4077349 [PubMed - indexed for MEDLINE]
|
Hemopoietic
effects of the reticuloendothelial agent glucan were assayed in normal mice and in mice hemopoietically depleted by
exposure to 60Co radiation. In normal mice,
glucan administration increased the content of bone marrow and splenic transplantable pluripotent hemopoietic stem
cells (CFU-s), committed granulocyte-macrophage progenitor
cells (GM-CFC), and pure macrophage progenitor cells (M-CFC). Erythroid
progenitor cells (CFU-e) were increased only in the spleen. In sublethally
irradiated mice (650 rads), glucan increased the number of endogenous pluripotent hemopoietic stem cells (E-CFU)
when administered either before or after irradiation.
The most pronounced effects were observed when glucan was administered
1 day before, 1 h before, or 1 h after irradiation. In addition, the administration of glucan before lethal
irradiation (900 rads) enhanced survival. The most
significant results were seen when glucan was aministered 1 day prior to irradiation. The possibility of using agents
such as glucan to enhance hemopoietic reconstitution
and prevent septicemia following chemotherapy and/or radiotherapy is discussed. |
| Patchen
ML, MacVittie TJ.
Hemopoietic effects of intravenous soluble glucan administration.
J Immunopharmacol. 1986;8(3):407-25. PMID:
3760593 [PubMed - indexed for MEDLINE]
|
A
soluble form of the reticuloendothelial- and immune modulating agent
glucan (glucan-F) has been evaluated
for its effects on hemopoiesis. A single 5.0 mg intravenous
injection of glucan-F into C3H/HeN mice increased peripheral white blood
cellularity, bone marrow and splenic
cellularity, bone marrow and splenic granulocyte-macrophage progenitor
cell numbers (GM-CFC), and splenic pluripotent stem cell (CFU-s)
and erythroid progenitor cell (CFU-e) numbers. Serum levels of granulocyte-macrophage
colony stimulating activity (CSA) were also
elevated following glucan-F administration.
These hemopoietic responses correlate well with those previously shown
to be induced by intravenous administration of particulate glucan
(glucan-P). In contrast to glucan-P,
however, intravenous glucan-F administration has been shown not
to induce granuloma formation and severe hepatosplenomegaly, thus the
potential clinical use of glucan-F as a
hemopoietic stimulant is more likely than that of glucan-P. |
| Patchen
ML, MacVittie TJ.
Comparative effects of soluble and particulate glucans on
survival in irradiated mice.
J Biol Response Mod. 1986 Feb;5(1):45-60.
PMID: 3958754 [PubMed - indexed for MEDLINE]
|
The
survival-enhancing capabilities of particulate (P) and soluble (F) glucan,
a B-1,3 polyglycan biological response
modifier, were assayed in 60Co irradiated mice. Although
glucan-P was slightly more effective than glucan-F, both glucans
significantly enhanced survival in
otherwise lethally irradiated (9.0-11.0 Gy) C3H/HeN mice. Following
9.0 Gy, 60% of the glucan-P treated and 53% of the glucan-F treated mice exhibited long-term survival as opposed to 0%
of the radiation control mice. The survival-enhancing
effects of glucan-P and glucan-F decreased as the radiation dose increased
to 11.0 Gy. At higher radiation doses (e.g., 12.0 Gy) neither glucan preparation was capable of enhancing survival.
Both glucan-P and glucan-F enhanced the
recovery of peripheral blood white cell numbers, platelet numbers, and
hematocrit values. In addition, both
agents increased endogenous pluripotent hemopoietic stem cell
numbers in sublethally irradiated mice. Taken together, these results
demonstrate that both glucan-P and
glucan-F can significantly enhance survival in lethally irradiated mice.
However, these agents appear to function specifically by enhancing
hemopoietic recovery and are not
effective at radiation does also known to induce gastrointestinal damage. |
| Patchen
ML, MacVittie TJ, Brook I.
Glucan-induced hemopoietic and immune stimulation: therapeutic
effects in sublethally and lethally irradiated mice.
Methods Find Exp Clin Pharmacol. 1986 Mar;8(3):151-5.
PMID: 3713378 [PubMed - indexed for
MEDLINE]
|
The
hemopoietic effects of glucan, a beta 1,3 polyglycan biological response
modifier, were assayed in normal and
irradiated mice. In normal mice, glucan administration increased
the content of bone marrow and splenic transplantable pluripotent hemopoietic
stem cells (CFU-s), committed granulocyte-macrophage progenitor cells
(GM-CFC), and pure macrophage progenitor cells
(M-CFC). In mice partially hemopoietic
depleted by exposure to 6.5 Gy of 60Co irradiation glucan increased the
number of endogenous pluripotent hemopoietic
stem cells (E-CFU). The most pronounced
effects were observed when glucan was administered 1 day before irradiation.
In addition, the administration of glucan 1 day before lethal (9.0 Gy)
irradiation-enhanced survival. The enhanced
survival in glucan-treated mice in part appeared
to be mediated by an enhanced resistance to the surgence of enteric
opportunistic pathogens that occurs following
radiation-induced hemopoietic and immune
depression. |
| Patchen
ML, D'Alesandro MM, Brook I, Blakely WF,
MacVittie TJ.
Glucan: mechanisms involved in its "radioprotective"
effect.
J Leukoc Biol. 1987 Aug;42(2):95-105. PMID:
3036990 [PubMed - indexed for MEDLINE]
|
It has
generally been accepted that most biologically derived agents that are
radioprotective in the hemopoietic-syndrome
dose range (eg, endotoxin, Bacillus Calmette
Guerin, Corynebacterium parvum, etc) exert their beneficial properties by
enhancing hemopoietic recovery and hence, by
regenerating the host's ability to resist life-threatening
opportunistic infections. However, using glucan as a hemopoietic stimulant/radioprotectant,
we have demonstrated that host resistance to opportunistic infection
is enhanced in these mice even prior to the detection of significant
hemopoietic regeneration. This early enhanced
resistance to microbial invasion in glucan-treated
irradiated mice could be correlated with enhanced and/or prolonged macrophage
(but not granulocyte) function. These results suggest that early after
irradiation glucan may mediate its
radioprotection by enhancing resistance to microbial invasion
via mechanisms not necessarily predicated on hemopoietic recovery. In
addition, preliminary evidence suggests that
glucan can also function as an effective free-radical
scavenger. Because macrophages have been shown to selectively phagocytize
and sequester glucan, the possibility that these specific cells may be
protected by virtue of glucan's scavenging
ability is also suggested. |
| Patchen
ML, D'Alesandro MM, Chirigos MA, Weiss
JF.
Radioprotection by biological response
modifiers alone and in combination
with WR-2721.
Pharmacol Ther. 1988;39(1-3):247-54. Review.
No abstract available. PMID: 2849129
[PubMed - indexed for MEDLINE] |
Abstract
not available |
| Patchen
ML, Chirigos MA, Brook I.
Use of glucan and other immunopharmacological agents in the prevention
and treatment of acuteradiation injuries.
Fundam Appl Toxicol. 1988 Nov;11(4):573-4.
No abstract available. PMID: 3229582
[PubMed - indexed for MEDLINE] |
Abstract
not available. |
| Patchen
ML, MacVittie TJ, Jackson WE.
Postirradiation glucan administration enhances the radioprotective
effects of WR-2721.
Radiat Res. 1989 Jan;117(1):59-69. PMID:
2536480 [PubMed - indexed for MEDLINE]
|
Based
on murine survival studies, endogenous hemopoietic spleen colony formation
(E-CFU), and recovery of bone marrow and
splenic granulocyte-macrophage colony-forming cells
(GM-CFC), it was demonstrated that the postirradiation administration of
glucan, an immunomodulator and hemopoietic
stimulant, enhances the radioprotective effects
of WR-2721. LD50/30 dose reduction factors for mice treated with WR-2721
(200 mg/kg approximately 30 min before
irradiation), glucan (250 mg/kg approximately 1
h after irradiation), or both agents were 1.37, 1.08, and 1.52,
respectively. Enhanced survival in mice
treated with both agents appeared to be due in part to glucan's ability
to accelerate hemopoietic regeneration from
stem cells initially protected from radiation-induced
lethality by WR-2721. Following a 10-Gy radiation exposure, E-CFU numbers
in mice treated with saline, WR-2721, glucan, or both WR-2721 and glucan
were 0.05 +/- 0.03, 6.70 +/- 1.05, 0.95 +/-
0.24, and 33.90 +/- 2.96, respectively. Similarly,
bone marrow and splenic GM-CFC numbers were greater in mice treated
with both WR-2721 and glucan than in mice
treated with either agent alone. These results
demonstrated at least additive radioprotective effects when mice were
given WR-2721 prior to irradiation and
glucan following irradiation. These effects appeared to
depend on the sequential cell protection mediated by WR-2721 and
hemopoietic repopulation mediated by
glucan. |
| Patchen
ML, MacVittie TJ, Weiss JF.
Combined modality radioprotection: the use of glucan and
selenium with WR-2721.
Int J Radiat Oncol Biol Phys. 1990 May;18(5):1069-75.
PMID: 2161407 [PubMed - indexed for
MEDLINE]
|
Glucan,
WR-2721, and selenium, three agents with distinct radioprotective mechanisms,
were evaluated in C3H/HeN mice for survival-enhancing and hemopoietic-regenerating
effects when administered alone or in combinations before exposure
to 60Co radiation. At LD50/30 radiation doses (radiation doses lethal for
50% of mice within 30 days postexposure), dose
reduction factors of 1.21, 1.02, 1.37, 1.51,
and 1.66 were obtained following glucan (75 mg/kg i.v., -20 hr), selenium
(0.8 mg/kg, i.p., -20 hr), WR-2721 (200
mg/kg, i.p., -30 min), glucan + WR-2721, and glucan
+ selenium + WR-2721 treatments, respectively. All treatments increased
numbers of hemopoietic stem cells as measured
by the day 12 endogenous spleen colony-forming
unit (E-CFU) assay; the most significant E-CFU effects, however, were
observed following glucan + WR-2721 and glucan
+ selenium + WR-2721 treatments. Combined
modality treatments were also more effective than single-agent treatments
at accelerating bone marrow and splenic
granulocyte-macrophage colony-forming cell (GM-CFC)
regeneration. These results demonstrate the value of multiple-agent
radioprotectants. |
| Patchen
ML, MacVittie TJ, Solberg BD, Souza LM.
Survival enhancement and hemopoietic regeneration following
radiation exposure: therapeutic approach using glucan and granulocyte
colony-stimulating factor.
Exp Hematol. 1990 Oct;18(9):1042-8. PMID:
1697806 [PubMed - indexed for MEDLINE]
|
C3H/HeN
female mice were exposed to wholebody cobalt-60 radiation and administered
soluble glucan (5 mg i.v. at 1 h following exposure), recombinant human
granulocyte colony-stimulating factor (G-CSF;
2.5 micrograms/day s.c., days 3-12 following
exposure), or both agents. Treatments were evaluated for their ability to
enhance hemopoietic regeneration, and to
increase survival after radiation-induced myelosuppression.
Both glucan and G-CSF enhanced hemopoietic regeneration alone;
however, greater effects were observed in mice receiving both agents. For
example, on day 17 following a sublethal
6.5-Gy radiation exposure, mice treated with saline,
G-CSF, glucan, or both agents, respectively, exhibited 36%, 65%, 50%, and
78% of normal bone marrow cellularity, and
84%, 175%, 152%, and 212% of normal splenic
cellularity. At this same time, granulocyte-macrophage colony-forming cell
(GM-CFC) values in saline, G-CSF, glucan, or
combination-treated mice, respectively, were
9%, 46%, 26%, and 57% of normal bone marrow values, and 57%, 937%, 364%,
and 1477% of normal splenic values. Endogenous
spleen colony formation was also increased
in all treatment groups, with combination-treated mice exhibiting the
greatest effects. Likewise, although both
glucan and G-CSF alone enhanced survival following
an 8-Gy radiation exposure, greatest survival was observed in mice treated
with both agents. These studies suggest that
glucan, a macrophage activator, can synergize
with G-CSF to further accelerate hemopoietic regeneration and increase
survival following radiation-induced
myelosuppression. |
| Baker
WH, Nold JB, Patchen ML, Jackson WE.
Histopathologic effects of soluble glucan and WR-2721, independently
and combined in C3H/HeN mice.
Proc Soc Exp Biol Med. 1992 Nov;201(2):180-91.
PMID: 1329111 [PubMed - indexed for
MEDLINE]
|
Soluble
glucan, an immunomodulator, and Walter Reed (WR)-2721, a radioprotectant,
increase postirradiation survival when
administered before and after exposure, respectively.
Combined, these agents act synergistically through WR-2721's ability to
spare hematopoietic stem/progenitor cells from
radiation injury and glucan's ability to subsequently
stimulate spared cells to proliferate. In this study, the histopathologic
effects of WR-2721 (200 mg/kg, ip) and glucan
(250 mg/kg, iv), at doses capable of increasing
survival in lethally irradiated mice, were evaluated in unirradiated and
irradiated female C3H/HeN mice. After
treatment, whole body weights and wet organ weights
of liver, spleen, and kidney, as well as gross and histologic changes in
these and other tissues, were monitored
on Days 1, 4, 7, 11, 15, 21, and 28. Morphometric studies
of splenic white and red pulps were also performed. Soluble glucan, with
or without WR-2721, in unirradiated
groups, was associated with splenomegaly, transient morphometrically
determined perturbations of white and red pulp areas, and histologic
alterations of white pulp. In irradiated mice,
splenic weight loss was initially dampened in
glucan groups and accompanied by morphologic and histologic changes
similar to those seen in unirradiated
counterparts. The subsequent rebound of splenic parameters
in irradiated mice was limited to WR-2721-treated mice and was associated
with hematopoietic reconstitution. Glucan, with or without WR-2721, in
unirradiated groups was associated with
transient hepatomegaly and associated histologic
changes. Similar changes in irradiated animals were seen only in the
combined treatment group. |
| Patchen
ML, MacVittie TJ, Solberg BD, D'Alesandro
MM, Brook I.
Radioprotection by polysaccharides alone and in combination
with aminothiols.
Adv Space Res. 1992;12(2-3):233-48. PMID:
11537014 [PubMed - indexed for MEDLINE]
|
We
demonstrated that glucan, a beta-1,3 polysaccharide immunomodulator,
enhances survival of mice when
administered before radiation exposure. Glucan's prophylactic survival-enhancing
effects are mediated by several mechanisms including (1) increasing
macrophage-mediated resistance to potentially lethal postirradiation
opportunistic infections, (2) increasing the
D(o) of hematopoietic progenitor cells, and (3)
accelerating hematopoietic reconstitution. In addition, even when
administered shortly after some
otherwise lethal doses of radiation, glucan increases survival. Glucan's
therapeutic survival-enhancing effects are also mediated through its
ability to enhance macrophage function
and to accelerate hematopoietic reconstitution; glucan's
therapeutic potential, however, is ultimately dependent on the survival of
a critical number of hematopoietic stem
cells capable of responding to glucan's stimulatory
effects. Preirradiation administration of the traditional aminothiol
radioprotectants WR-2721 and WR-3689 has been
previously demonstrated to be an extremely
effective means to increase hematopoietic stem cell survival. Therapeutic
glucan treatment administered in combination
with preirradiation WR-2721 or WR-3689 treatment
synergistically increases both hematopoietic reconstitution and survival.
Such combined modality treatments offer new promise in treating acute
radiation injury. |
| Patchen
ML, Brook I, Elliott TB, Jackson WE.
Adverse effects of pefloxacin in irradiated
C3H/HeN mice: correction with
glucan therapy.
Antimicrob Agents Chemother. 1993 Sep;37(9):1882-9.
PMID: 8239601 [PubMed - indexed for MEDLINE]
|
Opportunistic
bacterial infections are the predominant cause of death following myelosuppressive
radiation exposure. When used alone, a variety of immunomodulators
and antibiotics have been reported to reduce radiation-induced death.
In these studies, the combined therapeutic effects of the immunomodulator
glucan and the quinolone antibiotic pefloxacin
were evaluated for survival-enhancing effects
in myelosuppressed C3H/HeN mice. Mice were exposed to 7.9 Gy of whole-body
60Co radiation and treated with saline, glucan
(250 mg/kg of body weight intravenously,
1 h after irradiation), pefloxacin (64 mg/kg/day orally, days 3 to 24
after irradiation), or glucan plus
pefloxacin. Survival 30 days after irradiation in mice receiving
these respective treatments was 25, 48, 7, and 85%. Evaluation of granulocyte-macrophage
progenitor cell (GM-CFC) recovery in mice receiving these treatments
revealed that, compared with recovery in saline-treated mice, glucan
stimulated GM-CFC recovery, pefloxacin
suppressed GM-CFC recovery, and glucan administered
in combination with pefloxacin could override pefloxacin's hemopoietic
suppressive effect. |
| Hofer
M, Pospisil M.
Glucan as stimulator of hematopoiesis
in normal and gamma-irradiated
mice. A survey of the
authors' results.
Int J Immunopharmacol. 1997 Sep-Oct;19(9-10):607-9. PMID:
9637361 [PubMed - indexed for MEDLINE]
|
Glucan,
a beta-1,3-linked polyglucose derived from the yeast Saccharomyces cerevisiae,
is a broad spectrum enhancer of host defense mechanisms stimulating
humoral and cell-mediated immunity. On the
basis of these features, glucan has been tested
by the authors' research group in experiments on gamma-irradiated mice.
Two glucan forms, particulate and
soluble, have been studied. Attention has been focused on
various application regimens in relation to the time of irradiation (pre-
or postirradiation application), the
possibilities of using glucan in various radiation regimens
(single or repeated irradiation), combined pharmacological therapy (joint
administration of glucan with cystamine or
inhibitors of prostaglandin synthesis), and on
the negative side effects of therapy with glucan. Some studies included
also experiments on unirradiated mice.
The results have demonstrated the ability of glucan to
influence positively the course of the acute radiation disease.
Stimulation of hematopoiesis has been
found to be the most important mechanism of glucan's radioprotective
effects. In this communication, the results of 11 full-length articles are
summarized and discussed. |
|
