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Biomedical subjects

H Moll

Publications and source records attributed to H Moll.

At least 91 records · Page 5Linked to original sources
PubMed1989

A phosphodiester bridge between two arabinose residues as a structural element of an extracellular glycoprotein of Volvox carteri.

The sulphated glycoprotein SSG 185 is the monomeric precursor of a highly aggregated structural element in the extracellular matrix of the multicellular green alga Volvox carteri. A phosphodiester of arabinose was isolated from a saccharide fragment of SSG 185. The structure of this phosphodiester was investigated by methylation analysis, 13C-NMR, photometric methods and enzymatic assays and identified as D-Araiota-5-phospho-5-D-Araiota. The function of this phosphodiester bridge as a crosslink of different carbohydrate chains in SSG 185 is discussed.

Arabinose↗
PubMed1989

L3T4+ T cells promoting susceptibility to murine cutaneous leishmaniasis express the surface marker Ly-24 (Pgp-1).

In a murine model of cutaneous leishmaniasis, the importance of T cell-dependent immunity has been documented by the susceptibility to parasite infection of athymic nude mice of both genetically resistant and genetically susceptible strains. T lymphocytes from uninfected mice have the capacity to promote resistance to Leishmania major infection in nude recipients, whereas T cells from mice chronically infected with L. major not only fail to mediate protection, but totally abrogate the host-protective effect of normal mouse lymphocytes. Both these effects are mediated by T cells which have the phenotype L3T4+Ly-2-. To discriminate between the two activities, we have tried to separate the L3T4+ population on the basis of additional cell surface markers and we have found that peripheral L3T4+ lymphocytes could be subdivided according to their expression of the Ly-24 (Pgp-1) surface marker. In adoptive transfer experiments, both the Ly-24+ and the Ly-24- subset of L3T4+ cells from uninfected mice had the capacity to mediate resistance to infection with L. major. However, disease-promoting activity was only found in the L3T4+Ly-24+ and not in the L3T4+Ly-24- subset of cells from mice with chronic cutaneous disease. Moreover, Ly-24 expression was strongly increased in lymphocytes from chronically infected mice and in vitro limiting dilution analysis confirmed that the vast majority of L. major-reactive T cells was L3T4+Ly-24+. In genetically susceptible mice with chronic cutaneous leishmaniasis, Ly-24 therefore appears to be a marker for lymphocytes with the capacity to abrogate resistance to disease, these cells being activated and expanding in the course of progressive L. major infection. Ly-24 expression is a useful tool for phenotypic identification and selective enrichment of antigen-activated and possibly memory T cells. It may facilitate the isolation of L. major-specific T cell clones with defined activities.

Animals↗
PubMed1989

Monoclonal antibodies reacting with Schistosoma japonicum eggs and their target epitopes.

Ten monoclonal antibodies (McAbs) raised to Schistosoma japonicum eggs could be assigned using several serological and immunochemical techniques to 3 groups. The McAbs, termed A, B and C-McAbs, apparently recognize carbohydrate epitopes that can be located on the same antigen molecule. The antibodies, generally of IgM isotype, are idiotypically related. They are distinct from another IgM McAb (Group D-McAb) the carbohydrate target epitope of which can also be associated with the epitopes of A, B and C-McAbs. The McAbs produce large vacuolated bleb reactions in the circumoval precipitin test (COPT) and target epitopes have different representations in various life cycle stages such as immature and mature eggs, male and female worms (including S. mansoni). Antigens affinity purified on columns containing A, B, C and D-McAbs stimulate proliferation of T cells from egg-sensitized mice and elicit DTH reactions in such mice. This raises the possibility that the target antigens of these carbohydrate-reactive monoclonal antibodies are immunopathologic and involved in egg-induced granuloma formation.

Animals↗
PubMed1989

Evidence of T-cell recognition in mice of a purified lipophosphoglycan from Leishmania major.

We have previously reported that a Leishmania major lipophosphoglycan (LPG), given with killed Corynebacterium parvum as an adjuvant, can vaccinate mice against cutaneous leishmaniasis. In order to analyze whether T cells are able to recognize this important parasite antigen, we have studied both humoral and cellular immune responses to L. major LPG that had been isolated from promastigotes by sequential solvent extraction and hydrophobic chromatography. The data show that immunization of mice with highly purified LPG induced an increase in frequency of L. major-reactive T cells and the production of immunoglobulin G antibodies to LPG. Furthermore, genetically resistant mice infected with L. major were able to develop a specific delayed-type hypersensitivity response in the ear to L. major LPG. These findings strongly suggest that T cells can recognize and respond to glycolipid antigens, in this case a host-protective Leishmania LPG, even though such antigens appear not to be potent T-cell stimulators in mice.

Animals↗
PubMed1989

[Parasitic evasion mechanisms: Leishmania as an example].

Leishmania display a variety of mechanisms for effective evasion of the humoral and cellular immune responses of the host which are strongly associated with the expression of two major surface glycoconjugates, gp63 and lipophosphoglycan. The parasites are poor activators of the alternative complement pathway thus avoiding their own extracellular lysis. Complement bound on the surface of promastigotes promotes the uptake of leishmania by macrophages which function as "safe targets" as long as they are not activated by T lymphocytes. This is due to the fact that intracellular parasites are able to 1. decrease the oxidative burst; 2. scavenge toxic oxygen metabolites; 3. inhibit degradative lysosomal enzymes; 4. exploit the acidic milieu of lysosomes for their own metabolism. Finally, leishmania have been shown to evade the host's cellular immune response by down-regulating T cell-activating processes and by initiating the expansion of T cell subpopulations which promote their own survival.

Animals↗
PubMed1988

The transplantation barrier of nude mice.

Syngeneic memory cells can be stimulated to yield a secondary immune response after their transfer into irradiated euthymic recipients as well as into young thymusless nude mice. It is shown that nude mice older than twelve weeks of age are not permissive towards memory cell activation as it is found in non-irradiated euthymic animals. This barrier to isogeneic or congeneic cells seems to be caused by a pool of cyclophosphamide-sensitive cells. Since young nude mice could be rendered as unpermissive as older nude mice by pretreatment with either PNA-agglutinable thymus cells or nylon-wool passed spleen cells, it is suggested that an increased number of precursor T cells in older nude mice might induce this effect. Further experiments with monoclonal antibodies against the Lyt-1, Lyt-2, and L3T4 marker on T cells indicate that T-helper/inducer activity might be required to establish the "isogeneic barrier" in nude mice.

Aging↗
PubMed1988

Resistance to cutaneous leishmaniasis in nude mice injected with L3T4+ T cells but not with Ly-2+ T cells.

The importance of T cells in resistance to infection with the intracellular protozoan parasite Leishmania major is substantiated by the susceptibility to infection of athymic nude mice of both resistant and susceptible strains. However, the relative roles of different T cell subpopulations remain controversial. In order to address this issue, selected L3T4+ Ly-2- or L3T4- Ly-2+ T cell subpopulations from normal mice were adoptively transferred into athymic nude recipients of the same strain, and their capacity to mediate host-protective immunity against infection with L. major promastigotes was determined. In experiments with mice of different inbred strains, reconstitution with L3T4+ Ly-2- cells rendered the nude mice completely resistant to cutaneous leishmaniasis, whereas L3T4- Ly-2+ cells failed to do so. Partial protection in some recipients of large numbers of Ly-2+ cells could be ascribed to contamination of the transferred inoculum with L3T4+ cells. Thus, resistance to L. major infection in reconstituted nude mice can be promoted by L3T4+ T cells in the absence of detectable Ly-2+ T cells.

Animals↗
PubMed1988

Analysis of variables associated with promotion of resistance and its abrogation in T cell-reconstituted nude mice infected with Leishmania major.

Upon intradermal challenge with the protozoan parasite Leishmania major, some mouse strains develop chronic cutaneous lesions, whereas other mouse strains show a resolving pattern of disease. The importance of T cell-dependent immunity in resistance to cutaneous leishmaniasis is substantiated by the susceptibility to infection of athymic nude mice of both resistant and susceptible strains. Small numbers of T lymphocytes from uninfected euthymic mice promote resistance in nude mice but T cells from chronically infected mice can impair this protective effect. In the present study we used an adoptive transfer system in which nude mice were reconstituted with T cells from normal or chronically infected mice in order to further investigate protection against disease or disease promotion. The results supported the following conclusions: (a) the host-protective activity of T cells from uninfected mice is highly effective even in long-term chronically infected nude mice, (b) T cell-mediated exacerbation of cutaneous disease does not involve enhancement of lesion development and is thus unlikely to be based on an accelerated proliferation of parasites in the lesion, (c) disease-promoting cells are not only found in genetically susceptible mice but can also be induced in genetically resistant mice, and (d) lymphoid organs of genetically susceptible mice chronically infected with L. major contain resistance-promoting cells in addition to disease-promoting cells. The data, together with those of others, continue to support the notion that recruitment with expansion and/or activation of different T cell subsets underlies genetically based resistance and susceptibility of mice to L. major.

Animals↗
PubMed1987

Metabolism of exogenous arachidonic acid by mouse peritoneal macrophages.

On incubation of resident mouse peritoneal macrophages with arachidonic acid several hydroxyacyl derivatives detectable in cellular supernatants are formed. As main products monohydroxyarachidonic acids (monoHETE's) were identified. In addition, smaller amounts of dihydroxyarachidonic acids (diHETE's) were formed. A detailed analysis of cell culture supernatants by reversed phase HPLC, normal phase HPLC in combination with UV-spectroscopy and combined gas-chromatography/masspectrometry revealed the presence of 5-, 8-, 12- and 15- monoHETE's, two distinct 5,12-diHETE's, several 8,15-diHETE's and 14,15-diHETE. Among the 5,12-diHETE's, only small amounts of a compound with the characteristics of LTB4 were detected. Under the conditions employed, the cyclooxygenase products PGE2 and PGI2 (as 6-keto-PGF1 alpha) were only minor metabolites. In contrast, when macrophage cultures were stimulated with the phagocytic stimulus zymosan, PGI2, PGE2 and LTC4 were found as the major conversion products of arachidonic acid, whereas mono- and diHETE's were not formed in detectable amounts.

Animals↗
PubMed1986

Characterization and isolation of a trypsin-like serine protease from a long-term culture cytolytic T cell line and its expression by functionally distinct T cells.

We describe the characterization and purification of a trypsin-like serine protease isolated from cloned long-term culture cytolytic T cell line (CTLL AK). High amounts of proteolytic activity were isolated from extracts of CTLL AK after either nitrogen cavitation or detergent lysis. Trypsin-like protease was detected by using either the ester compound N alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester or a panel of low molecular amide substrates. The latter compounds were preferentially cleaved at the carboxyl termini of lysine and arginine residues. The enzyme activity was completely inhibited by two serine esterase inhibitors, diisopropylfluorophosphate and phenylmethanesulfonyl fluoride, and by aprotinin and meta-aminobenzamidine, which are known to block trypsin-like proteases. The pH optimum for CTLL AK-derived protease activity is 8 to 9. Analysis of the enzyme by gel filtration revealed that the cell-bound proteolytic activity was associated with a complex that could not be dissociated by treatment with Triton X-100. The CTLL AK-derived protease activity was found to reside in two proteins with relative molecular masses (Mr) of 32,000 and 40,000 daltons as determined by affinity labeling with [3H]diisopropylfluorophosphate and sodium dodecyl sulfate gel electrophoresis. High levels of enzyme activity were found in a panel of H-Y-specific cloned T cell lines with either cytolytic/suppressor (CTLL) or helper potential (THL), indicating a lack of correlation between trypsin-like protease activity and a particular T cell function. High enzyme activity was also detected in tumorigenic variants of CTLL. Furthermore, it was excluded that the trypsin-like activity detected was attributable to plasminogen activator activity. In contrast to cloned T effector cells and their in vitro or in vivo derived variants, considerably less activity was found in normal nonactivated or activated lymphocyte populations. The possible role of the trypsin-like serine protease in the function of T effector cells is discussed.

Animals↗
PubMed1985

Structural analysis of underivatized sialic acids by combined high-performance liquid chromatography-mass spectrometry.

Mass spectra of chemically ionized, positive ions of underivatized N,O-acylated sialic acids, 2-deoxy-2,3-didehydro-N-acetylneuraminic acid and sialyl-alpha(2-3)-lactose were obtained by combined high-performance liquid chromatography--mass spectrometry, using a direct liquid inlet system. The mass spectra of the different compounds for which fragmentation schemes are proposed enable the differentiation between sialic acids, although the localization of O-substituents is not possible. However, since the various sialic acids separated well on high-performance liquid chromatography, combined high-performance liquid chromatography-mass spectrometry allowed their unequivocal characterization.

Animals↗