Anti-complementary action of polymorphic “solubility forms” of particulate inulin

Cooper, Penny; Carter, Margrit

doi:10.1016/0161-5890(86)90075-1

Cited by 57 publications

(51 citation statements)

References 18 publications

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“…To deplete GPS of alternative complement pathway activity, the serum was incubated with 7-inulin (0.5 mg/ml) at 37 °C for 30 min as described by Cooper & Carter (1986). Inulin was removed by centrifugation in a microfuge (5 min, 4 °C) and the supernatant was stored at -70 °C.…”

Section: Methodsmentioning

confidence: 99%

Complement-dependent neutralization of influenza virus by a serum mannose-binding lectin

Anders

Hartley

Reading

et al. 1994

Journal of General Virology

123

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Section: Methodsmentioning

confidence: 99%

Complement-dependent neutralization of influenza virus by a serum mannose-binding lectin

Anders

Hartley

Reading

et al. 1994

Journal of General Virology

123

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“…Adjuvancity of inulin was linked to the activation of the complement cascades [50]. Structurally, inulin occurred in various isoforms a, b, g and d. Out of these, g inulin was proven to be a powerful adjuvant in immune activation [18].…”

Section: Natural Polymersmentioning

confidence: 99%

Applications of polymeric adjuvants in studying autoimmune responses and vaccination against infectious diseases

Shakya

Nandakumar

2013

J. R. Soc. Interface.

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Polymers as an adjuvant are capable of enhancing the vaccine potential against various infectious diseases and also are being used to study the actual autoimmune responses using self-antigen(s) without involving any major immune deviation. Several natural polysaccharides and their derivatives originating from microbes and plants have been tested for their adjuvant potential. Similarly, numerous synthetic polymers including polyelectrolytes, polyesters, polyanhydrides, non-ionic block copolymers and external stimuli responsive polymers have demonstrated adjuvant capacity using different antigens. Adjuvant potential of these polymers mainly depends on their solubility, molecular weight, degree of branching and the conformation of polymeric backbone. These polymers have the ability not only to activate humoral but also cellular immune responses in the host. The depot effect, which involves slow release of antigen over a long duration of time, using different forms (particulate, solution and gel) of polymers, and enhances the co-stimulatory signals for optimal immune activation, is the underlying principle of their adjuvant properties. Possibly, polymers may also interact and activate various toll-like receptors and inflammasomes, thus involving several innate immune system players in the ensuing immune response. Biocompatibility, biodegradability, easy production and purification, and non-toxic properties of most of the polymers make them attractive candidates for substituting conventional adjuvants that have undesirable effects in the host.

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“…This was first recognized with discovery of GI, which was sharply demarcated (Cooper and Steele 1991) and distinct from the poorly characterizable alpha inulin (AI). GI only formed from higher DP fractions isolated by gel exclusion chromatography (Cooper and Carter 1986a), so that the "higher" GI variant did indeed comprise longer polymer chains than AI, and DI had analogous higher DP properties .…”

Section: Introductionmentioning

confidence: 99%

“…Micro-particulate inulin (MPI) was originally developed (Cooper and Carter 1986a) as an anti-cancer therapeutic based on the premise that in vivo alternative pathway complement activation may have anti-tumor effects (Cooper and Masinello 1983;Cooper and Sim 1984;Cooper 1985). The first therapeutic isoform (gamma inulin (GI)) was followed by the more active delta inulin (DI), which is the clinically preferred option .…”

Section: Introductionmentioning

confidence: 99%

The polysaccharide inulin is characterized by an extensive series of periodic isoforms with varying biological actions

2013

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In studying the molecular basis for the potent immune activity of previously described gamma and delta inulin particles and to assist in production of inulin adjuvants under Good Manufacturing Practice, we identified five new inulin isoforms, bringing the total to seven plus the amorphous form. These isoforms comprise the step-wise inulin developmental series amorphous → alpha-1 (AI-1) → alpha-2 (AI-2) → gamma (GI) → delta (DI) → zeta (ZI) → epsilon (EI) → omega (OI) in which each higher isoform can be made either by precipitating dissolved inulin or by direct conversion from its precursor, both cases using regularly increasing temperatures. At higher temperatures, the shorter inulin polymer chains are released from the particle and so the key difference between isoforms is that each higher isoform comprises longer polymer chains than its precursor. An increasing trend of degree of polymerization is confirmed by end-group analysis using 1 H nuclear magnetic resonance spectroscopy. Inulin isoforms were characterized by the critical temperatures of abrupt phase-shifts (solubilizations or precipitations) in water suspensions. Such (aqueous) "melting" or "freezing" points are diagnostic and occur in strikingly periodic steps reflecting quantal increases in noncovalent bonding strength and increments in average polymer lengths. The (dry) melting points as measured by modulated differential scanning calorimetry similarly increase in regular steps. We conclude that the isoforms differ in repeated increments of a precisely repeating structural element. Each isoform has a different spectrum of biological activities and we show the higher inulin isoforms to be more potent alternative complement pathway activators.

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Anti-complementary action of polymorphic “solubility forms” of particulate inulin

Cited by 57 publications

References 18 publications

Complement-dependent neutralization of influenza virus by a serum mannose-binding lectin

Complement-dependent neutralization of influenza virus by a serum mannose-binding lectin

Applications of polymeric adjuvants in studying autoimmune responses and vaccination against infectious diseases

The polysaccharide inulin is characterized by an extensive series of periodic isoforms with varying biological actions

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