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Effects of a soluble glucan on hemopoietic stem cell proliferation
273
THE STRUCTURAL DEPENDENCE OF ANTI-TUMOR EFFECT OF SCHIZOPHYLLAN T. Kojima, K. Tabata, and W. Itoh Research Laboratory, Tait,~ Co., Ltd. Na~ta-ku,
87
Kobe, 653, Japan.
Schizophyllan, a beta-l,3-glucan extracellularly elaborated by Schizoph211um commune Fries, has z prima~-y structure consisting of a main chain of only beta-l,5-glucopym'anosyl residues, of which one out of three sugar residues are attached with single glucopyranose residues at C-6 positions. This polysaccharide dissolved in water was proved to have a rod-like triple helix. The lower molecular weight schizophyllan prepared by appropriate ultrasonication, can be used effectively for cancer-immunotheraI~. The moderate depolymerization for clinical use of sonicated schizophyllan having molecular weight about 45×104 caused neither appreciable variation of the primary and conformational structures nor reduction in its anti-tumor activity. A depolymerization of schizophyllan by prolonged ultrasonic irradiation followed by fractionation afforded a series of schizophyllan-fra~ments having a variety of molecular weights lower than iOx104 . The relationship between chemical natures and the anti-tumor activities of the low molecular weightfragments and also of some chemically modified schizophyllans will be discussed.
CIRCUMSPOROZOITE PROTEINS. A FAMILY OF PROTECTIVE MALARIAL ANTIGENS
88
Ruth S. ~ s e r ~ e i a
Head, Division of Parasitology, Department of Microbiology, New York University School of Medicine, 550 First Avenue, New York, New York 100]6 USA Monoclonal antibodies against surface membrane antigens of sporozoites of rodent, simian and human malaria were found to neutralize, i.e. to abolish the i n f e c t i v i t y of these parasites. The circumsporozoite (CS) proteins, against which these monoclonals are directed, cover the entire surface of the sporozoites, but not of other developmental stages of Plasmodia. Sporozoites of the various Plasmodial species also contain two higher molecular weight intracellular precursors of the surface antigen. The biosynthetic physico-chemical and antigenic properties and the peptide maps of these various CS proteins and their precursors indicate that they are structurally related. I t is postulated that these polypeptides play an important role in sporozoite attachment and/or penetration into host cells. EFFECTS OF A SOLUBLE GLUCAN ON HEMOPOIETIC STEM CELL PROLIFERATION. M. Patchen and T. MacVittie Experimemtal Hematology Department, Armed Forces Radiobiology Research L'~stitute, Betheeda, M D Z0814 U S A
Particulate glucan~ obtained from the inner cell wall of the yeast Saccharom[ces cerevisiae, has b e e n shown to significantly a l t e r the prollferation of pluripQtent h e m o p o i e t i c s t e m ~ U - S ) , g r a n u l o c y t e - m a c r o p h a g e c o l o n y - f o r m i n g cells (GM--CFC) and e r y t h r o i d c o l o n y - f o r m i n g cells (CFU-e) in routine borne marrow (BM) and spleen ($PL). Here we report the h e m o p o i e t i c e f f e c t s of a soluble glucan prepared from the same y e a s t . F e m a l e C3H/HeN m i c e w e r e intravenously injected with 1.5 mg of glucan and Z, 5 and 13 days later the BM and SPL cellularity, CFU-$, GM-CFC and C F U - e were assayed. In comparison to control values, BM c e l l u l a r i t y i n c r e a s e d Z5% on day 13, while SPL cellularity i n c r e a s e d 30% and 100% on days 5 and !3. BM CFU-S and C F U - e were ~ot a l t e r e d after glucan administration. However, SPL CFU-S i n c r e a s e d 133% and 433% on days 5 and 13 and C F U - e i n c r e a s e d 2Z5%, Z50% and 350% on days Z, 5 and 13, r e s p e c t i v e l y . GM-CFC w e r e increased in both the BM and the SPL following glucan t r e a t m e n t with BM GM-CFC increasing 72% on day 13 and SPL GM-CFC increasing 169%, 200% and 352% on days Z, 5 and 13, r e s p e c t i v e l y . Although we conclude that soluble glucan can function as a potent hemopoietic modulator, its e f f e c t s on bone marrow CFU-S and CFU--e differ from the e f f e c t s of the s a m e dose of p a r t i c u l a t e glucan. These differences will b e discussed.
89
THE STRUCTURAL DEPENDENCE OF ANTI-TUMOR EFFECT OF SCHIZOPHYLLAN T. Kojima, K. Tabata, and W. Itoh Research Laboratory, Tait,~ Co., Ltd. Na~ta-ku,
87
Kobe, 653, Japan.
Schizophyllan, a beta-l,3-glucan extracellularly elaborated by Schizoph211um commune Fries, has z prima~-y structure consisting of a main chain of only beta-l,5-glucopym'anosyl residues, of which one out of three sugar residues are attached with single glucopyranose residues at C-6 positions. This polysaccharide dissolved in water was proved to have a rod-like triple helix. The lower molecular weight schizophyllan prepared by appropriate ultrasonication, can be used effectively for cancer-immunotheraI~. The moderate depolymerization for clinical use of sonicated schizophyllan having molecular weight about 45×104 caused neither appreciable variation of the primary and conformational structures nor reduction in its anti-tumor activity. A depolymerization of schizophyllan by prolonged ultrasonic irradiation followed by fractionation afforded a series of schizophyllan-fra~ments having a variety of molecular weights lower than iOx104 . The relationship between chemical natures and the anti-tumor activities of the low molecular weightfragments and also of some chemically modified schizophyllans will be discussed.
CIRCUMSPOROZOITE PROTEINS. A FAMILY OF PROTECTIVE MALARIAL ANTIGENS
88
Ruth S. ~ s e r ~ e i a
Head, Division of Parasitology, Department of Microbiology, New York University School of Medicine, 550 First Avenue, New York, New York 100]6 USA Monoclonal antibodies against surface membrane antigens of sporozoites of rodent, simian and human malaria were found to neutralize, i.e. to abolish the i n f e c t i v i t y of these parasites. The circumsporozoite (CS) proteins, against which these monoclonals are directed, cover the entire surface of the sporozoites, but not of other developmental stages of Plasmodia. Sporozoites of the various Plasmodial species also contain two higher molecular weight intracellular precursors of the surface antigen. The biosynthetic physico-chemical and antigenic properties and the peptide maps of these various CS proteins and their precursors indicate that they are structurally related. I t is postulated that these polypeptides play an important role in sporozoite attachment and/or penetration into host cells. EFFECTS OF A SOLUBLE GLUCAN ON HEMOPOIETIC STEM CELL PROLIFERATION. M. Patchen and T. MacVittie Experimemtal Hematology Department, Armed Forces Radiobiology Research L'~stitute, Betheeda, M D Z0814 U S A
Particulate glucan~ obtained from the inner cell wall of the yeast Saccharom[ces cerevisiae, has b e e n shown to significantly a l t e r the prollferation of pluripQtent h e m o p o i e t i c s t e m ~ U - S ) , g r a n u l o c y t e - m a c r o p h a g e c o l o n y - f o r m i n g cells (GM--CFC) and e r y t h r o i d c o l o n y - f o r m i n g cells (CFU-e) in routine borne marrow (BM) and spleen ($PL). Here we report the h e m o p o i e t i c e f f e c t s of a soluble glucan prepared from the same y e a s t . F e m a l e C3H/HeN m i c e w e r e intravenously injected with 1.5 mg of glucan and Z, 5 and 13 days later the BM and SPL cellularity, CFU-$, GM-CFC and C F U - e were assayed. In comparison to control values, BM c e l l u l a r i t y i n c r e a s e d Z5% on day 13, while SPL cellularity i n c r e a s e d 30% and 100% on days 5 and !3. BM CFU-S and C F U - e were ~ot a l t e r e d after glucan administration. However, SPL CFU-S i n c r e a s e d 133% and 433% on days 5 and 13 and C F U - e i n c r e a s e d 2Z5%, Z50% and 350% on days Z, 5 and 13, r e s p e c t i v e l y . GM-CFC w e r e increased in both the BM and the SPL following glucan t r e a t m e n t with BM GM-CFC increasing 72% on day 13 and SPL GM-CFC increasing 169%, 200% and 352% on days Z, 5 and 13, r e s p e c t i v e l y . Although we conclude that soluble glucan can function as a potent hemopoietic modulator, its e f f e c t s on bone marrow CFU-S and CFU--e differ from the e f f e c t s of the s a m e dose of p a r t i c u l a t e glucan. These differences will b e discussed.
89