Biomedical subjects

M Leippe

Publications and source records attributed to M Leippe.

42 records · Page 3Linked to original sources

PubMed1992

[Recent findings on the pathogenicity of Entamoeba histolytica].

Entamoeba histolytica is the causative agent of human amoebiasis. During recent years, research in amoebiasis has concentrated on two subjects: 1. the dual manifestation of the infection as harmless colonization of the intestinal cavity or pathogenic tissue invasion and 2. the molecular analysis of functions of E. histolytica that are considered essential for pathogenicity. Besides epidemiological studies and isoenzyme analyses, molecular genetics have revealed additional evidence that two genetically distinct forms of E. histolytica do exist, named "pathogenic" and "nonpathogenic" forms, respectively. Both can infect humans but only the "pathogenic" form is able to invade the tissue and cause disease whereas the "nonpathogenic" is not. Questions remain open about the mechanism that triggers "pathogenic" E. histolytica to become invasive and about the molecules that are involved. Current data indicate that at least three functions of the amoebae are considered essential for pathogenic tissue invasion. Pathogenicity is viewed as a result of 1. adherence of the amoeba to host cells, predominantly mediated by a galactose- and N-acetylgalactosamine-inhibitable lectin, 2. killing of host cells by a pore-forming peptide known as amoebapore, and 3. proteolysis of the host's extracellular matrix mediated by cysteine proteinases. Structural detailed molecular analysis including cloning of the corresponding genes have led to a better understanding of the function of these proteins.

Animals↗

PubMed1991

Pore-forming peptide of pathogenic Entamoeba histolytica.

A polypeptide that causes pore formation in target-cell membranes is implicated in the potent cytolytic activity of pathogenic Entamoeba histolytica. Pore-forming material was purified to apparent homogeneity by a multistep procedure, and its analysis by NaDodSO4/PAGE revealed one peptide of 4-5 kDa under nonreducing or under reducing conditions. Pore-forming activity was measured by depolarization of liposome membrane potential and was found to be optimally expressed at low pH. Active material preferentially inserted into negatively charged lipid vesicles. Treatment of purified amoeba peptide in solution or bound to liposomes with glutaraldehyde revealed oligomers upon NaDodSO4/PAGE, suggesting functionally relevant peptide-peptide interactions. The NH2-terminal amino acid sequence of the amoeba peptide was determined by protein sequencing and revealed a structural similarity to melittin, the membranolytic peptide of bee venom.

Amino Acid Sequence↗

PubMed1991

Two major serum components antigenically related to complement factor H are different glycosylation forms of a single protein with no factor H-like complement regulatory functions.

Factor H is a 150-kDa serum glycoprotein with key regulatory functions in the alternative pathway of complement activation. Two glycoproteins with a molecular mass of approximately 42 and 37 kDa that react with an antiserum against factor H were purified from human plasma. The two glycoproteins have identical N-terminal amino acid sequences but differ in glycosylation. Sequence comparisons indicated that they both correspond to a 1.4-kb mRNA recently cloned from human liver cDNA. The serum concentration of the two glycoproteins together was estimated to be approximately 40 mg/liter. They were found not to exert factor H-like regulatory functions in the alternative pathway. Thus, the 42-kDa glycoprotein described here appears to be distinct from the previously characterized factor H-related protein of similar size, suggesting that human serum contains two factor-H related molecules which both have a molecular mass of 41 to 43 kDa but which differ largely in structure.

Amino Acid Sequence↗

PubMed1988

Release of cytotoxic and agglutinating molecules by Mytilus hemocytes.

Hemolymph of Mytilus edulis is known to contain cytotoxic hemocytes and a serum agglutinin. This study describes the occurrence of strong hemolytic properties as well as agglutinating activity of a hemocyte extract against different types of erythrocytes. The hemolysin purified by preparative disc-electrophoresis and subjected to PAGE reveals one band which is also visible in the electropherogram of the extract or serum, respectively. Likewise, the serum agglutinin corresponds to another distinct fraction of extract and serum. Both, hemolytic and agglutinating molecules are detectable in the supernatant of a short-term hemocyte culture indicating that these substances are actively secreted by Mytilus blood cells.

Agglutinins↗

PubMedDate not supplied

Antimicrobial and cytolytic polypeptides of amoeboid protozoa--effector molecules of primitive phagocytes.

Amoebae are primitive, actively phagocytosing eukaryotic cells, many of which use bacteria as a major nutrient source. One may suppose that amoebae possess an array of potent antimicrobial molecules acting in synergy to combat bacterial growth inside their phagosomes. Lysosome-like granular vesicles of Entamoeba histolytica contain a family of 77-residue peptides with a compact alpha-helical, disulfide-bonded fold. These polypeptides, named amoebapores, exhibit antibacterial and cytolytic activity by forming pores in membranes of various origin. It is of particular interest that amoebapores are structurally and functionally most similar to polypeptides of mammalian cytotoxic lymphocytes. In addition, amoebic granules contain bacteriolytic proteins with lysozyme-like properties. Some amoebic polypeptides may represent archaic analogs of effector molecules from invertebrates and vertebrates.

Amino Acid Sequence↗

PubMedDate not supplied

Comparative modeling of amoebapores and granulysin based on the NK-lysin structure-structural and functional implications.

Amoebapores, the pore-forming polypeptides of the protozoan parasite Entamoeba histolytica, and effector proteins of porcine and human lymphocytes, namely NK-lysin and granulysin, reveal a substantial sequence similarity despite their enormous evolutionary distance. Moreover, all these polypeptides display antibacterial activity and are in higher concentrations cytolytic to eukaryotic cells. The recently solved NMR structure of NK-lysin enabled us to build the three dimensional structures of amoebapores and granulysin by comparative modeling. The generated models revealed the expected similarities, but also fundamental differences with respect to charge distribution, hydrophobicity and core packing. The combination of these structural properties and known biochemical data provides insight in the different membrane-interacting mechanisms of the proteins. For amoebapores, exposed hydrophobic grooves and a locally loosely packed protein core may allow a rearrangement of the protein and therefore may account for its ability to penetrate the target membrane and to form defined ion channels in planar lipid bilayers. In contrast, the structural features of NK-lysin and granulysin appear to be suitable for a membrane-perturbing mode of action rather than for channel formation.

Amino Acid Sequence↗