Recombinant form of human wild type mannan-binding lectin (MBL/A) but not its structural variant (MBL/C) promotes phagocytosis of zymosan by activating complement.

Mannan-binding lectin (MBL) mediates innate immune responses, such as activation of the complement lectin pathway and phagocytosis, to help fight infections. In the present study, employing recombinant forms of human MBL (rMBL), the role of wild type MBL (rMBL/A) and its structural variant rMBL/C in mediating THP-1 phagocytosis of fluorescent-labeled zymosan was examined and compared to MBL purified from human plasma (pMBL/A). Flow cytometric analyses revealed that opsonization of zymosan with rMBL/A and pMBL/A (0.

Stringent regulation of complement lectin pathway C3/C5 convertase by C4b-binding protein (C4BP).

The complement lectin pathway, an essential component of the innate immune system, is geared for rapid recognition of infections as each C4b deposited via this pathway is capable of forming a C3/C5 convertase. In the present study, role of C4b-binding protein (C4BP) in regulating the lectin pathway C3/C5 convertase assembled on zymosan and sheep erythrocytes coated with mannan (E(Man)) was examined. While the C4BP concentration for inhibiting 50% (IC(50)) formation of surface-bound C3 convertase on the two surfaces was similar to that obtained for the soluble C3 convertase (1.

New insights on the structural/functional properties of recombinant human mannan-binding lectin and its variants.

Inefficient activation of complement lectin pathway in individuals with variant mannan-binding lectin (MBL) genotypes has been attributed to poor formation of higher order oligomers by MBL. But recent studies have shown the presence of large oligomers of MBL (approximately 450 kDa) in serum of individuals with variant MBL alleles. The recombinant forms of MBL (rMBL) variants except MBL/B that assemble into higher order oligomers have not yet been reported.

Activation of complement component C5: comparison of C5 convertases of the lectin pathway and the classical pathway of complement.

Although the initiating complex of lectin pathway (called M1 in this study) generates C3/C5 convertases similar to those assembled by the initiating complex (C1) of the classical pathway, activation of complement component C5 via the lectin pathway has not been examined. In the present study kinetic analysis of lectin pathway C3/C5 convertases assembled on two surfaces (zymosan and sheep erythrocytes coated with mannan (E(Man))) revealed that the convertases (ZymM1,C4b,C2a and E(Man)M1,C4b,C2a) exhibited a similar but weak affinity for the substrate, C5 indicated by a high K(m) (2.73-6.

Relevance of radioprotectors in radiotherapy: studies with tocopherol monoglucoside.

Radioprotective compounds are of importance in clinical radiation therapy, because normal tissues should be protected against radiation injury while using higher doses of radiation to obtain better cancer control. We investigated the radioprotection of cellular DNA in cancer and in various cells and tissues, in a murine system following exposure to gamma-radiation and tocopherol monoglucoside (TMG) administration. We used single-cell gel electrophoresis (comet assay) and studied the progression of murine fibrosarcoma following radiation exposure and administration of TMG.

Radiosensitizer sanazole (AK-2123) enhances gamma-radiation-induced apoptosis in murine fibrosarcoma.

Sanazole (AK-2123) (N-2'-methoxy ethyl)-2-(3"-nitro-1"-triazolyl)acetamide, which has completed phase III clinical trials as a radiosensitizer, enhanced gamma-radiation induced apoptosis in murine fibrosarcoma upon i.p. administration at 40 mg/kg body weight one hour prior to irradiation.

Effect of vinblastine sulfate on gamma-radiation-induced DNA single-strand breaks in murine tissues.

The effect of vinblastine sulfate on gamma-radiation-induced DNA strand breaks in different tissues of tumour bearing mice, was studied by single-cell gel electrophoresis. Intraperitonial administration of different doses (0.25-2.

Inhibition of gamma-radiation induced DNA damage in plasmid pBR322 by TMG, a water-soluble derivative of vitamin E.

Alpha-tocopherol monoglucoside (TMG), a water-soluble derivative of alpha-tocopherol, has been examined for its ability to protect DNA against radiation-induced strand breaks. Gamma radiation, up to a dose of 6 Gy (dose rate, 0.7 Gy/minute), induced a dose-dependent increase in single strand breaks (SSBs) in plasmid pBR322 DNA.