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M W Russell

Publications and source records attributed to M W Russell.

At least 127 records · Page 7Linked to original sources
PubMed1986

Analysis of the hepatobiliary transport of IgA with monoclonal anti-idiotype and anti-allotype antibodies.

The processing and fate of mixed immune complexes is influenced by the antibody isotypes present. The hepatobiliary transport of mixed immune complexes containing the mouse IgA myeloma protein J558 and corresponding monoclonal IgG or IgM anti-J558 idiotype or monoclonal IgG anti-mouse IgA allotype antibodies has been studied. The anti-idiotype or anti-allotype antibodies were radiolabeled and injected into mice with or without mouse polymeric IgA (J558). IgG anti-idiotype antibodies to J558 IgA were selectively transported into bile by J558 IgA. This process occurred with a radiolabeled Fab preparation of the IgG anti-idiotype and was inhibitable with IgA of an irrelevant antigenic specificity. Thus, polymeric IgA influenced the fate of IgA-IgG idiotype-anti-idiotype serum immune complexes. A monoclonal anti-idiotype antibody of the IgM isotype (D8-3) was not selectively transported into bile by itself or as an IgA-IgM complex. A monoclonal IgG antibody (CB5-6) to a mouse allotype determinant in the Fc portion of IgA was not selectively transported into bile. This anti-allotype monoclonal antibody inhibited the hepatobiliary transport of 125I-polymeric J558 IgA and therefore appeared to directly or indirectly block the site in the Fc region of IgA recognized by the hepatic receptor.

Animals↗
PubMed1986

Detection and specificity of antibodies secreted by spleen cells in mice immunized with Streptococcus mutans.

Immune responses of mice to Streptococcus mutans serotype c were analyzed by means of the enzyme-linked immunospot assay to determine the predominant specificities of the antibodies developed. In general, the numbers of splenic antibody-secreting cells correlated with serum antibody levels. A low dose (10(8) CFU) of killed whole cells injected twice intraperitoneally induced antibodies mainly against surface protein antigen I/II. A higher dose (10(9) CFU) given two to six times also resulted in a predominance of antigen I/II antibody-secreting cells and, in addition, antibody responses to surface protein antigen III and lipoteichoic acid occurred. Cells producing antibodies to serotype c polysaccharide were elicited only on repeated immunization. These results agreed with the development of antibodies in rabbits repeatedly immunized intravenously with killed whole cells of S. mutans, S. rattus, and S. sobrinus, which induced specific antibodies in accordance with the surface antigens that they express. Mice immunized twice with the same dose of purified antigens I/II and III developed greater numbers of antigen I/II splenic antibody-forming cells than antigen III splenic antibody-forming cells and higher serum antibody levels to antigen I/II than to antigen III. Furthermore, a single injection of antigen I/II but not of antigen III was sufficient to induce a strong specific-antibody response. Some evidence was also obtained for weak polyclonal stimulation of spleen cells by S. mutans cells and by antigen I/II, a result which could be relevant to the induction by S. mutans of antibodies reactive with mammalian tissues. It was concluded that for the antigens examined, S. mutans elicited the strongest antibody response against antigen I/II, which was also highly immunogenic in purified form.

Animals↗
PubMed1986

IgA subclasses.

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Amino Acid Sequence↗
PubMed1986

Potential for immunological intervention against dental caries.

Potentiation of the host immune system has been considered, in addition to non-immunological measures as a means of preventing the development of dental caries. Because specific antibodies in the oral cavity are derived from two sources--the salivary glands that produce secretory IgA, and the general circulation that provides IgG antibodies--immunization efforts in various experimental models have been aimed at stimulating either of these compartments. Streptococcus mutans, the principal cariogenic microorganism, and various cell wall components and extracellular enzymes have been used as antigens. In experimental animals, systemic or oral routes of immunization have induced protective IgG or IgA antibodies respectively, but the mechanisms of protection have not been clearly established. The possibility of stimulating a generalized secretory immune response by oral ingestion of antigens may have advantages for the induction of protective antibodies in humans, because parenteral immunization routes may not be readily acceptable for reasons discussed in this review. Nevertheless, further experimental work is required to select appropriate antigens, and to determine optimal doses and immunization schedules for inducing antibodies at an age that is critical in the development of dental caries.

Animals↗
PubMed1984

Light-scattering investigation of the subunit structure and dissociation of Helix pomatia hemocyanin. Effects of salts and ureas.

The effects of various salts of the Hofmeister and aliphatic acid salt series and hydrophobic reagents of the urea series on the subunit structure and the dissociation of Helix pomatia alpha-hemocyanin were investigated by employing light-scattering molecular weight methods. In moderate ranges of salt concentrations [0-1.0 M NaClO4, NaSCN, NaI, and guanidinium chloride (GdmCl) and 0-2.0 M NaBr], the dissociation reaction is essentially a two-step process characterized by the dissociation of whole hemocyanin molecules dissociating to half-molecules of decamers followed by the dissociation of the half-molecules to five dimeric fragments. The effectiveness of the salts and relative ineffectiveness of the ureas and GdmCl as dissociating agents in the first step of the dissociation reaction suggest that the stabilization of the contact areas between half-molecules in solution is largely a nonhydrophobic energy process involving polar and ionic interactions. Hydrophobic forces appear to be important, however, for stabilization of the half-molecules through side to side contacts of the five dimeric units that make up each half-molecule. The analysis of our dissociation data by use of equations derived in our previous studies [Herskovits, T. T., & Harrington, J.P. (1975) Biochemistry 14, 4964-4971] gave apparent estimates of amino acid groups of about 60-150 for each of the contact areas between the cylindrically shaped half-molecules and 30-60 for each of the dimers in the half-molecules themselves.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Selective hepatobiliary transport of human polymeric IgA in mice.

Both subclasses of human polymeric IgA (pIgA) were selectively transported from the serum into the bile of mice relative to human IgG or IgM. Removal of human pIgA from serum corresponded to the clearance kinetics shown for murine pIgA. The biliary pIgA was intact as determined by sucrose density gradient ultracentrifugation. This hepatic uptake was specific for the IgA isotype and occurred independently of receptors in the liver specific for glycoproteins that terminate with galactose or mannose moieties. Desialylation of human pIgA resulted in its rapid clearance from serum and subsequent deposition in the liver in a manner similar to most other desialylated serum glycoproteins. The desialylated pIgA present in bile was also an intact molecule; thus the asialoglycoprotein receptor may represent an additional mechanism for the transport of serum pIgA into bile.

Animals↗
PubMed1984

Elimination of intestinally absorbed antigen into the bile by IgA.

Polymeric serum IgA has been shown to transport antigens in the form of IgA immune complexes from the circulation into the bile. To test the hypothesis that this mechanism could aid in the clearance of intestinally absorbed antigens, mice were gastrically intubated with trinitrophenylated human serum albumin (TNP-HSA). After 3 hr, two groups were injected i.v. with either MOPC 315 (IgA, anti-TNP) or control ascitic fluid. One hour later, blood and bile samples were taken. Small amounts of antigen (0.0008% of the intubated dose) were detected in the serum of control animals by solid phase radioimmunoassay. In animals receiving anti-TNP IgA, serum levels were decreased significantly and intact antigen appeared in the bile, whereas no antigen was detectable in the bile of control mice. These results suggest that IgA-mediated hepatobiliary transport can function as one of the mechanisms for the elimination of intestinally absorbed antigens.

Animals↗
PubMed1983

Immunoglobulin A-mediated hepatobiliary transport constitutes a natural pathway for disposing of bacterial antigens.

The possibility that hepatobiliary transport of immunoglobulin A (IgA) immune complexes might eliminate bacterial antigens was investigated in mice with pneumococcal type III capsular polysaccharide and C carbohydrate and corresponding monoclonal antibodies. Although all isotypes of antibody caused uptake by the liver, only IgA, but not IgG or IgM, antibodies transported these substances into bile where they were detected in the form of immune complexes and as free antigens. Small doses (10 micrograms or less) of passively administered IgA antibody were sufficient to induce measurable transport of capsular polysaccharide into bile. Transport of C carbohydrate was significantly correlated with the level of naturally occurring IgA antibodies specific for the phosphocholine determinant, but not with IgM or IgG antibodies. These results suggest that the continual process of hepatic uptake of circulating polymeric IgA may function to eliminate bacterial macromolecular products that are not readily susceptible to other mechanisms of disposal.

Animals↗
PubMed1983

IgA-mediated elimination of antigens by the hepatobiliary route.

Polymeric IgA antibody mediates the transport of corresponding antigens, in the form of IgA immune complexes (IC), from the circulation into the bile, whereas monomeric IgA, IgG, and IgM are ineffective. Transport has been shown with dinitrophenyl albumin and bacterial polysaccharides such as pneumococcal SIII and C-substance. The process does not result in breakdown of the antigen, which can be detected in the bile in intact free and IgA-bound forms. Although IgG promotes clearance of antigen from the circulation mainly to the liver, only low levels of breakdown fragments are detectable in bile. In mice, the mechanism of IgA IC transport does not appear to involve Kupffer cells, the complement system, or the glycoprotein receptors on liver cells because attempts to block these systems failed to affect transport. The mechanism appears to be analogous to that for free IgA. Transport could be inhibited by antigen-nonspecific IgA, but not IgG or IgM. IgA IC were found in the bile but not in the saliva, milk, urine, or bronchial or intestinal washings. A similar pattern of appearance was seen when IgA alone was injected. Thus hepatobiliary transport appears to be the major pathway for the clearance of both IgA IC and free IgA from the circulation.

Animals↗
PubMed1982

Preferential transport of IgA and IgA-immune complexes to bile compared with other external secretions.

When radiolabeled dinitrophenyl-human serum albumin was injected intravenously in mice together with M315 IgA, labeled antigen was specifically transported into bile, but not into saliva, urine, milk or bronchial and intestinal secretions. Ultracentrifugal analysis showed that the antigen transported into bile was intact and partly complexed with IgA. The radioactivity that was present in other secretions regardless of M315 IgA, represented free and degraded fragments of antigen. M315 IgA alone was readily transported into bile, where it was detected at high titer by hemagglutination, but not into other secretions, apart from milk which contained only very low titers. The liver therefore appears to be singularly capable of transporting both free and complexed IgA into its secretion, the bile.

Animals↗
PubMed1982

Hepatobiliary transport of IgA immune complexes: molecular and cellular aspects.

The molecular and cellular parameters of the transport of IgA immune complexes (IgA-IC) from the circulation to the bile in vivo were studied in mice. Polymeric MOPC 315 IgA was effective in the transport of 125I-DNP-HSA into the bile, whereas complexes containing monomeric IgA were not transported. The transport to IgA-IC could be blocked by excess from IgA of different antigen specificity, but not by IgG or IgM. Hepatobiliary transport did not appear to involve the galactose- or mannose-specific glycoprotein receptors of the liver. No differences in IgA-IC transport, relative to controls, could be seen in mice that had been treated with cobra venom factor or whose mononuclear phagocytic system had been blockaded with colloidal carbon. These data suggested that the hepatobiliary transport of IgA-IC proceeds by a mechanism similar to the selective transport of free polymeric IgA through the hepatocyte.

Animals↗
PubMed1981

Role of serum IgA. Hepatobiliary transport of circulating antigen.

The IgA mediated hepatobiliary excretion of antigen from the circulation was studied using a radiolabeled haptenated protein (dinitrophenyl-human serum albumin) injected intravenously in mice together with monoclonal anti-dinitrophenyl antibodies of different immunoglobulin classes. Antibodies were obtained from ascitic fluids of mice bearing the MOPC315 myeloma (IgA), or immune spleen cell hybridomas (IgG and IgM). IgA antibody brought about the transport of large amounts of antigen from the circulation to the bile during 1-3h. Analysis of bile by gel filtration showed that a large part of the transported antigen remained intact and complexed with IgA. Neither IgA of different specificity nor anti-dinitrophenyl IgM medicated biliary transport of antigen. With anti-dinitrophenyl IgG, only small amounts of low molecular weight fragments of labeled antigen were found in he bile. Preformed immune complex of radiolabeled antigen and IgA antibody were rapidly transported from the circulation to the bile, resulting in threefold-higher levels of radioactivity in bile than in serum. It is proposed that an important function of serum IgA is to mediate the hepatobiliary excretion of corresponding circulating antigens.

Animals↗
PubMed1981

Immunization with purified protein antigens from Streptococcus mutans against dental caries in rhesus monkeys.

Protein antigens I, I/II, II, and III were prepared from Streptococcus mutans (serotype c). Their immunogenicities and protective effects against dental caries were investigated in 40 rhesus monkeys kept entirely on a human-type diet, containing about 15% sucrose. Antigens I, I/II and, to a lesser extent, antigen II induced significant reductions in dental caries, as compared with sham-immunized monkeys. This was achieved with 1 or 2 doses of antigen, the first of which was administered with adjuvant (Freund incomplete adjuvant or aluminum hydroxide). There was no reduction in caries in monkeys immunized with antigen III. The reduction in caries in the animals immunized with antigens I or I/II was comparable to that in monkeys immunized with whole cells. Protection against caries was associated predominantly with serum and gingival crevicular fluid immunoglobulin G antibodies, which appeared to be directed against the antigen I determinant, but antibodies to antigen II, though not to antigen III, were also protective.

Animals↗
PubMed1980

Immunisation with a purified protein from Streptococcus mutans against dental caries in rhesus monkeys.

A purified protein antigen, molecular weight 185,000, was prepared from Streptococcus mutans and used in the immunisation of monkeys against dental caries. 1 mg of this antigen, mixed with adjuvant and injected subcutaneously, elicited serum IgG and to a lesser extent IgA antibodies. Compared with sham-immunised monkeys, those receiving this antigen had a 70% reduction in dental caries and a smaller growth of Strep. mutans from dental plaque. The results suggest that the defined protein material isolated from Strep. mutans may be one of the antigens eliciting a protective immune response against dental caries. This antigen seems to be a suitable candidate for consideration as a vaccine for man.

Animals↗
PubMed1980

Protein antigens of Streptococcus mutans: purification and properties of a double antigen and its protease-resistant component.

A surface protein antigen of Streptococcus mutans having two sets of antigenic determinants (antigens I and II) was purified by column chromatography from culture supernatants of S. mutans serotype c. The protease-resistant component, antigen II, was purified from pronase-digested antigen I/II. The antigens were analyzed chemically and immunologically, and their physicochemical properties were investigated. Antigen I/II consisted of more than 80% protein, and its peptide chain molecular weight was estimated to be 185,000. Antigen II consisted of approximately 60% protein, with a peptide chain molecular weight of 48,000. Antisera to antigens I/II and II were raised in rabbits and used to investigate the presence of the antigens in cells of other streptococci. This indicated that not only serotype c but also serotypes e and f possessed antigen I and II determinants, whereas serotypes a, d, and g possessed a determinant related to antigen I but not one related to antigen II.

Amino Acids↗
PubMed1980

Affinity purification and characterization of protease-susceptible antigen I of Streptococcus mutans.

An antigenic component (antigen I) of the cell surface of Streptococcus mutans has been purified from culture supernatants and shown to be immunologically identical to the protease-susceptible moiety of antigen I/II. Ion-exchange and gel filtration chromatography failed to yield a physicochemically homogeneous product. Immunoasbsorbent chromatography on single and tandem columns containing immobilized antibodies to antigens I/II and II yielded identical products which were homogeneous in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and which when injected into rabbits induced monospecific antisera to antigen I. This antigen consisted of approximately 70% protein. Its molecular weight was estimated as 150,000, and the isoelectric point was estimated to be 5.1. Immunofluorescence microscopy using monospecific antiserum to antigen I showed that a similar antigen was present on cells of S. mutans serotypes a, c, d, e, f, and g, but not b.

Animals↗