lactoferrin and Lymphoma

In order to further evaluate the effects of rGM-CSF on the reconstituting granulopoiesis, plasma and serum levels of myeloperoxidase (MPO) and lactoferrin (LF), as well as serum levels of eosinophil cationic protein (ECP), were monitored daily during a period of 3-4 weeks following ABMT in a group of 22 patients treated with either rGM-CSF (n = 11) or placebo (n = 11). Despite faster increase in the neutrophil counts in the rGM-CSF group, we did not observe any difference either in P-MPO or in P-LF during the period of early engraftment (days 11-19). This finding indicates that the proliferative effect of rGM-CSF on the neutropoiesis may be overestimated when neutrophil counts alone are taken into consideration, and suggests that other mechanisms may have contributed to the increase in the number of circulating neutrophils. The ratio of the serum to plasma level of LF, but not of MPO, was higher in the rGM-CSF group, probably reflecting a specific in vivo neutrophil priming effect. In the rGM-CSF group there was a clear increase of S-ECP during the second and third week post transplant, corresponding to an increase in eosinophil counts, which indicates that rGM-CSF stimulated eosinophil reconstitution without causing excessive activation of the mature eosinophils.

Topics: Adolescent; Adult; Blood Proteins; Bone Marrow Transplantation; Double-Blind Method; Eosinophil Granule Proteins; Eosinophils; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoiesis; Humans; Lactoferrin; Leukocyte Count; Lymphoma; Middle Aged; Multiple Myeloma; Neutrophils; Peroxidase; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recombinant Proteins; Ribonucleases

Cationic antimicrobial peptides (CAPs) with antitumor activity constitute a promising group of novel anticancer agents. These peptides induce lysis of cancer cells through interactions with the plasma membrane. It is not known which cancer cell membrane components influence their susceptibility to CAPs. We have previously shown that CAPs interact with the two glycosaminoglycans (GAGs), heparan sulfate (HS) and chondroitin sulfate (CS), which are present on the surface of most cells. The purpose of this study was to investigate the role of the two GAGs in the cytotoxic activity of CAPs.. Various cell lines, expressing different levels of cell surface GAGs, were exposed to bovine lactoferricin (LfcinB) and the designer peptide, KW5. The cytotoxic effect of the peptides was investigated by use of the colorimetric MTT viability assay. The cytotoxic effect on wild type CHO cells, expressing normal amounts of GAGs on the cell surface, and the mutant pgsA-745, that has no expression of GAGs on the cell surface, was also investigated.. We show that cells not expressing HS were more susceptible to CAPs than cells expressing HS at the cell surface. Further, exogenously added heparin inhibited the cytotoxic effect of the peptides. Chondroitin sulfate had no effect on the cytotoxic activity of KW5 and only minor effects on LfcinB cytotoxicity.. Our results show for the first time that negatively charged molecules at the surface of cancer cells inhibit the cytotoxic activity of CAPs. Our results indicate that HS at the surface of cancer cells sequesters CAPs away from the phospholipid bilayer and thereby impede their ability to induce cytolysis.

Topics: Animals; Cattle; Cell Line, Tumor; Chlorates; CHO Cells; Cricetinae; Cricetulus; Drug Synergism; Heparin; Heparitin Sulfate; HT29 Cells; Humans; Lactoferrin; Lymphoma; Neoplasms; Peptide Fragments; Protein Structure, Secondary

The effect of a bovine milk protein, lactoferrin (bLf), and a pepsin-generated peptide of bLf, lactoferricin (Lfcin-B), on inhibition of tumor metastasis produced by highly metastatic murine tumor cells, B16-BL6 melanoma and L5178Y-ML25 lymphoma cells, was examined in experimental and spontaneous metastasis models using syngeneic mice. The subcutaneous (s.c.) administration of bovine apo-lactoferrin (apo-bLf) and Lfcin-B 1 day after tumor inoculation significantly inhibited liver and spleen metastasis of L5178Y-ML25 cells and lung metastasis of B16-BL6 cells, whereas human apo-lactoferrin (apo-hLf) and bovine holo-lactoferrin (holo-Lf) at the dose of 1 mg/mouse did not. Furthermore, both apo-bLf and Lfcin-B, but not apo-hLf and holo-bLf, inhibited the number of tumor-induced blood vessels and suppressed tumor growth on day 8 after tumor inoculations in an in vivo model. However, in a long-term analysis of tumor growth for up to 21 days after tumor inoculation, single administration of apo-bLf significantly suppressed the growth of B16-BL6 cells throughout the examination period, but Lfcin-B showed inhibitory activity only during the early period (8 days). In spontaneous metastasis model, multiple administration of both apo-bLf and Lfcin-B significantly inhibited lung metastasis of B16-BL6 cells, however it was only apo-bLf that exhibited the inhibitory effect of tumor growth at the time of primary tumor amputation (on day 21) after tumor inoculation. The results suggest that apo-bLf and Lfcin-B inhibit tumor metastasis through different mechanisms, and that the inhibitory activity of bLf on tumor metastasis may be related to the property of iron (Fe3+)-saturation.

Topics: Animals; Antineoplastic Agents; Cattle; Humans; Lactoferrin; Lymphoma; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Neoplasm Metastasis; Neovascularization, Pathologic

Central nervous system (CNS) involvement in patients with leukaemia or lymphoma presents a diagnostic problem. This study was conducted to test whether combined measurements of various cellular markers such as beta 2-microglobulin (beta 2m), lactoferrin (LF) and lysozyme (LYS) in the cerebrospinal fluid (CSF) might aid in the diagnosis of CNS involvement in such patients. Forty-two patients were studied. Sixteen were considered to have CNS involvement and 26 showed no signs of such involvement. In the group with symptoms or signs of CNS involvement, nine patients out of 12 had increased total protein in CSF, 14 of 14 increased beta 2m, 14 of 16 increased LYS and five of 15 increased LF. In patients without CNS involvement total protein was increased in four of 25, beta 2m in three of 21, LYS in four of 28 and LF in one of 28 patients. The differences were statistically significant (P less than 0.01, P less than 0.001, P less than 0.001 and P less than 0.05, respectively). Prophylactic intrathecal methotrexate treatment in patients with acute lymphoblastic leukaemia caused an increase in the CSF of beta 2m, LYS and LF but not of total protein, which may reflect a drug-induced inflammatory reaction in the CNS. We conclude that combined measurements of the three cell markers add to our understanding of the cellular reaction to malignant cells in the CNS in leukaemia and lymphoma and may be valuable supplements in the diagnosis of this CNS involvement.

Topics: Adolescent; Adult; Aged; beta 2-Microglobulin; Central Nervous System Diseases; Female; Humans; Injections, Spinal; Lactoferrin; Lactoglobulins; Leukemia; Lymphoma; Male; Methotrexate; Middle Aged; Muramidase; Time Factors

The distribution of iron and iron binding proteins (IBP) have been compared with control spleen tissue in an attempt to establish a pattern of staining restricted to Hodgkin's disease (HD). All but one of the HD spleens examined stained for ferritin, which was largely present in red pulp dendritic macrophages (DM). In spleens histologically involved with HD heavy deposits of ferritin were seen around tumour nodules. Staining for ferritin increased with involvement of the spleen in HD but DM still represented the bulk of positive cells. However, ferritin positive DM were frequently seen in control spleens, and often in large numbers. Staining of ferric iron by Perls technique was less prominent than ferritin but this observation was also true of the non-HD spleens studied. Patterns of staining with transferrin were equivalent in both groups of spleens with DM being the most frequently positive cell type. Polymorphous macrophages showing erythrophagocytosis were present in the red pulp sinuses of all groups of spleens and although these cells have been considered as precursors of the Reed-Sternberg cell their presence seemed related to total splenic ferritin regardless of the disease process. These cells marked as macrophages and their presence was not restricted to HD. The results show that there is no particular appearance of iron or IBP distribution which is restricted to HD spleens. However, staining for ferritin and iron increased in HD spleens with tumour involvement and could contribute to circulatory abnormalities in this disease.

Topics: Ferritins; Hodgkin Disease; Humans; Iron; Lactoferrin; Lymphoma; Macrophages; Spleen; Thalassemia; Transferrin

In the present paper we apply the "ecotaxis hypothesis" to the analysis of lymphocyte distribution in Hodgkin's disease and other forms of lymphoid malignancy. The results lead us to consider the possiblity that metal-binding proteins, namely ferritin, transferrin and lactoferrin, play a role in lymphocyte ecotaxopahty. It is suggested that in Hodgkin's disease, a failure of lymph node and spleen monocytes to handle iron normally could explain most of the hematologic, immunologic, pathologic, and epidemiologic features of the disease.

Topics: Cell Movement; Female; Ferritins; Hodgkin Disease; Humans; Iron; Lactoferrin; Leukemia; Lymph Nodes; Lymphoma; Male; Monocytes; Phagocytosis; Receptors, Antigen, B-Cell; Rosette Formation; Spleen; Splenectomy; Splenic Neoplasms; T-Lymphocytes; Transferrin