Association of lactoferrin with specific granules in rabbit heterophil leukocytes
01 Mar 1970-Journal of Experimental Medicine (The Rockefeller University Press)-Vol. 131, Iss: 3, pp 559-570
TL;DR: Leukocyte lactoferrin was found to be exclusively localized in the specific (secondary) granules, which have been resolved from other subcellular components by zonal differential centrifugation and by isopycnic equilibration.
Abstract: Lactoferrin has been identified in rabbit heterophil leukocytes on the basis of its immunological reactivity, electrophoretic mobility, acid-resistant iron-binding properties, and spectral characteristics. Leukocyte lactoferrin was found to be exclusively localized in the specific (secondary) granules, which have been resolved from other subcellular components by zonal differential centrifugation and by isopycnic equilibration.
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TL;DR: The OX26 monoclonal antibody against the rat transferrin receptor offers great promise in the delivery of therapeutic agents across the blood-brain barrier to the brain and serves as a potential alternative to viral vector for gene therapy.
Abstract: The membrane transferrin receptor-mediated endocytosis or internalization of the complex of transferrin bound iron and the transferrin receptor is the major route of cellular iron uptake. This efficient cellular uptake pathway has been exploited for the site-specific delivery not only of anticancer drugs and proteins, but also of therapeutic genes into proliferating malignant cells that overexpress the transferrin receptors. This is achieved either chemically by conjugation of transferrin with therapeutic drugs, proteins, or genetically by infusion of therapeutic peptides or proteins into the structure of transferrin. The resulting conjugates significantly improve the cytotoxicity and selectivity of the drugs. The coupling of DNA to transferrin via a polycation or liposome serves as a potential alternative to viral vector for gene therapy. Moreover, the OX26 monoclonal antibody against the rat transferrin receptor offers great promise in the delivery of therapeutic agents across the blood-brain barrier to the brain.
1,000 citations
Cites background from "Association of lactoferrin with spe..."
...Ovotransferrin (oTf) is found in avian and reptilian oviduct secretions and in avian egg white (Jeltsch and Chambon, 1982; Williams et al., 1982), and lactoferrin (Lf) is found in milk, tear, saliva, and other secretions (Baggiolini et al., 1970; Metzboutigue et al., 1984)....
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Journal Article•
876 citations
TL;DR: The findings indicate that the situation is basically the same as described previously in the rabbit, insofar as the origin, enzymic activity, and persistence in the mature cell of the two types of granules are concerned.
Abstract: Neutrophilic leukocytes (PMN) and their precursors from normal human marrow and blood were examined by histochemical staining and by electron microscopy and cytochemistry in order to determine the origin and nature of their cytoplasmic granules. Human neutrophils contain two basic types of granules, azurophils and specifics, which differ in morphology, contents, and time of origin. Azurophils are large and may be spherical or ellipsoid, the latter with a crystalline inclusion. They are produced in the first secretory stage (promyelocyte), contain peroxidase and various lysosomal enzymes, and thus correspond to modified primary lysosomes. Specifics are smaller, may be spherical or elongated, and are formed during a later secretory stage (myelocyte). They lack lysosomal enzymes and contain alkaline phosphatase and basic protein; their contents remain largely undetermined. Specifics outnumber azurophils in the mature PMN because of reduction in numbers of azurophils per cell by cell division in the myelocyte stage. The findings indicate that the situation is basically the same as described previously in the rabbit, insofar as the origin, enzymic activity, and persistence in the mature cell of the two types (azurophil and specific) of granules are concerned. The main difference between PMN of the two species is in the morphology (size, shape, and density) of the granules, especially the azurophils.
840 citations
TL;DR: Streptococcus mutans and Vibrio cholerae, but not Escherichia coli, were killed by incubation with purified human apolact oferrin, contingent upon the metal-chelating properties of the lactoferrin molecule.
Abstract: Streptococcus mutans and Vibrio cholerae, but not Escherichia coli, were killed by incubation with purified human apolactoferrin. Concentrations of lactoferrin below that necessary for total inhibition resulted in a marked reduction in viable colony-forming units. This bactericidal effect was contingent upon the metal-chelating properties of the lactoferrin molecule.
665 citations
TL;DR: Particular organisms are susceptible to more than one antimicrobial system and thus may be effectively handled by back-up systems when one is absent, and an organism normally killed by the peroxidase system may be handled less efficiently but adequately when MPO is absent by other oxygen-dependent antimicrobial systems.
593 citations
References
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TL;DR: By standardizing the technical conditions of the experiment it is possible to use this principle for the immunochemical determination of antigens, and the lower limit of the method was found to correspond to 0·0025 μg of antigen, and to an antigen concentrations of 1·25 μg per ml.
8,937 citations
TL;DR: Improved, largely automated methods are described for the purification and analysis of peroxisomes, lysosomes, and mitochondria from the livers of rats injected with Triton WR-1339, making more conclusive and precise previous estimates of the biochemical and morphological properties of the three groups of cytoplasmic particles.
Abstract: Improved, largely automated methods are described for the purification and analysis o peroxisomes, lysosomes, and mitochondria from the livers of rats injected with Triton WR-1339. With these new methods, it has become possible to obtain, in less than 6 hr and with reliable reproducibility, mitochondria practically free of contaminants, as well as the rarer cytoplasmic particles in amounts (about 100 mg of protein) and in a state of purity (95%) that make them suitable for detailed biochemical studies. The results obtained so far on these preparations have made more conclusive and precise previous estimates of the biochemical and morphological properties of the three groups of cytoplasmic particles. In addition, peroxisomes were found to contain essentially all the L-α-hydroxy acid oxidase of the liver, as well as a small, but significant fraction of its NADP-linked isocitrate dehydrogenase activity. Another small fraction of the latter enzyme is present in the mitochondria, the remainder being associated with the cell sap. The mitochondrial localization of the metabolically active cytoplasmic DNA could be verified. The relative content of the fractions in mitochondria, whole peroxisomes, peroxisome cores, lysosomes, and endoplasmic reticulum was estimated independently by direct measurements on electron micrographs, and by linear programming (based on the assumption that the particles are biochemically homogeneous) of the results of enzyme assays. The two types of estimates agreed very well, except for one fraction in which low cytochrome oxidase activity was associated with mitochondrial damage.
1,052 citations
TL;DR: Immunohistochemical data indicate that lactoferrin first appears in myeloid cells at the stage of the promyelocyte, and the identification of this protein in leukocyte extracts was based upon a comparison of its electrophoretic, antigenic, and iron-combining properties with the corresponding properties of the same protein isolated from human and guinea pig milk.
Abstract: Lactoferrin, an iron-binding protein previously shown to occur in many external secretions, is identified as one of the major proteins present in human and guinea pig neutrophilic polymorphonuclear leukocytes.
The identification of this protein in leukocyte extracts was based upon a comparison of its electrophoretic, antigenic, and iron-combining properties with the corresponding properties of the same protein isolated from human and guinea pig milk. Immunochemical quantitations showed that lactoferrin occurs in human neutrophilic leukocytes at the concentration of 3 µg per 106 cells. Tissue cultures from guinea pig bone marrow and spleen actively synthesized the protein, as shown both by net production of lactoferrin and incorporation of labeled amino acids into the protein. Immunohistochemical data indicate that lactoferrin first appears in myeloid cells at the stage of the promyelocyte.
641 citations
TL;DR: The iron-binding protein characteristic of milk, here called lactoferrin, has been demonstrated to occur in saliva, nasal secretions, tears, bronchial mucus, hepatic bile, pancreatic juice, seminal fluid, female cervical mucus and urines and it is suggested that it is of value in the defence of epithelial surfaces against infection.
575 citations
"Association of lactoferrin with spe..." refers background in this paper
...Lactoferrin is an iron-binding protein which occurs in milk and in many other biological fluids, such as tears, saliva, nasal and bronchial secretions, gastrointestinal juice, seminal fluid, cervical mucus, and urine, but not in serum (1, 2)....
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TL;DR: The results indicate that inversion of the azurophil/specific granule ratio occurs during the myelocyte stage and is due to: (a) reduction of azuro phil granules by multiple mitoses; (b) lack of new azuroPhil granule formation after the progranulocyte stage; and (c) continuing specific granule production.
Abstract: The origin, nature, and distribution of polymorphonuclear leukocyte (PMN) granules were investigated by examining developing granulocytes from normal rabbit bone marrow which had been fixed in glutaraldehyde and postfixed in OsO4. Two distinct types of granules, azurophil and specific, were distinguished on the basis of their differences in size, density, and time and mode of origin. Both types are produced by the Golgi complex, but they are formed at different stages of maturation and originate from different faces of the Golgi complex. Azurophil granules are larger (∼800 mµ) and more dense. They are formed only during the progranulocyte stage and arise from the proximal or concave face of the Golgi complex by budding and subsequent aggregation of vacuoles with a dense core. Smaller (∼500 mµ), less dense specific granules are formed during the myelocyte stage; they arise from the distal or convex face of the Golgi complex by pinching-off and confluence of vesicles which have a finely granular content. Only azurophil granules are found in progranulocytes, but in mature PMN relatively few (10 to 20%) azurophils are seen and most (80 to 90%) of the granules present are of the specific type. The results indicate that inversion of the azurophil/specific granule ratio occurs during the myelocyte stage and is due to: (a) reduction of azurophil granules by multiple mitoses; (b) lack of new azurophil granule formation after the progranulocyte stage; and (c) continuing specific granule production. The findings demonstrate the existence of two distinct granule types in normal rabbit PMN and their separate origins from the Golgi complex. The implications of the observations are discussed in relationship to previous morphological and cytochemical studies on PMN granules and to such questions as the source of primary lysosomes and the concept of polarity within the Golgi complex.
458 citations
"Association of lactoferrin with spe..." refers background in this paper
...These granules form two main groups that are synthesized at different stages in the maturation of the cells, and can be recognized by their cytochemical staining properties (15-20)....
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...This is when the specific granules are formed, whereas the azurophil granules develop at an earlier maturation stage (16, 17)....
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