The Evolution of the Secreted Regulatory Protein Progranulin.

Progranulin is a secreted growth factor that is active in tumorigenesis, wound repair, and inflammation. Haploinsufficiency of the human progranulin gene, GRN, causes frontotemporal dementia. Progranulins are composed of chains of cysteine-rich granulin modules.

Regulation of progranulin expression in myeloid cells.

Progranulin (pgrn; granulin-epithelin precursor, PC-cell-derived growth factor, or acrogranin) is a multifunctional secreted glycoprotein implicated in tumorigenesis, development, inflammation, and repair. It is highly expressed in macrophage and monocyte-derived dendritic cells. Here we investigate its regulation in myeloid cells.

Are there naturally occurring pleomorphic bacteria in the blood of healthy humans?

Dark-field microscopy of blood from healthy individuals revealed the existence of pleomorphic microorganisms. These bacteria exhibited limited growth and susceptibility to antibiotics and could be detected by fluorescent in situ hybridization and flow cytometry. They were further characterized by analysis of their 16S rRNA and gyrB genes.

Characterization and mapping to human chromosome 8q24.3 of Ly-6-related gene 9804 encoding an apparent homologue of mouse TSA-1.

The 9804 gene, which encodes a human Ly-6 protein most similar to mouse differentiation Ag TSA-1/Sca-2, has also been called RIG-E. Like mouse TSA-1, it has a broad tissue distribution with varied expression levels in normal human tissues and tumor cell lines. Like some members of the murine Ly-6 family, the 9804 gene is responsive to IFNs, particularly IFN-alpha.

Downregulation of adrenal atrial natriuretic peptide receptor mRNAs and proteins by pregnancy in rats.

The main objective of this study was to find out if the reported changes in the aldosterone-suppressant activity of atrial natriuretic peptide (ANP) during different hormonal states in rats are due to a modulation of ANP receptors. In zona glomerulosa cells, ribonuclease protection assay detected mRNAs for guanylate cyclase (GC)-coupled ANP GC-A and GC-B receptors, and for ANP C receptors, which are not coupled to GC. Western analysis using polyclonal anti-GC-A and anti-GC-B receptor antibodies revealed the presence of GC-A but not GC-B receptor proteins in zona glomerulosa cells.

Increased expression of proopiomelanocortin (POMC) mRNA in adrenal glands of mice undergoing graft-versus-host disease (GVHD): association with persistent elevated plasma corticosterone levels.

GVHD in animal models induces severe thymic atrophy as a result of prolonged secretion of high concentrations of adrenal glucocorticoids. In this study we investigated the mechanism responsible for the persistent stimulation of the adrenal glands to secrete glucocorticoids in mice undergoing GVHD. GVHD was induced across the major and multiple minor histocompatibility antigen difference in unirradiated C57Bl/6 x AF1 hybrid mice by the intravenous injection of A strain parental lymphoid cells.

Differential expression of corticostatins/defensins: higher levels of CS-4 (NP-2) transcripts compared with CS-6 (NP-5) in rabbit lung.

cDNA clones encoding two members of the corticostatin (CS)/defensin family of peptides have been isolated from a rabbit bone marrow cDNA library through cross-hybridization with cDNA encoding the human corticostatin HP-4. They encode the precursors of CS-4 (NP-2, MCP-2) and CS-6 (NP-5). Highly specific probes were generated for Northern blotting of RNA from various normal rabbit tissues.

The gene encoding the human corticostatin HP-4 precursor contains a recent 86-base duplication and is located on chromosome 8.

The human neutrophil-derived cationic peptide HP-4 exhibits corticostatic activity on adrenal cells and is an L-type calcium channel agonist at nanomolar concentrations. Complementary DNA clones encoding the HP-4 precursor have been isolated from a human bone marrow cDNA library by screening with oligonucleotide probes. The nucleotide sequence shares about 72% identity with the cDNA encoding defensin HP-1, but differs from it, and from other genes of this family characterized to date, by an extra 83-base segment.

Nucleotide sequence of the central coding region of bovine erythrotropin/insulin-like growth factor II cDNA from fetal intestine and northern analysis of the major IGF II transcripts at the time of hepatic erythropoiesis.

1. cDNA for insulin-like growth factor II (IGF II) was synthesized from poly A(+)-RNA from fetal bovine intestine and amplified. 2.

Isolation and sequence of the granulin precursor cDNA from human bone marrow reveals tandem cysteine-rich granulin domains.

Granulins are candidate growth factors recently discovered in human and rat inflammatory leukocytes and bone marrow. Two granulin homologs, epithelin 1 and 2, occur in the rat kidney. Epithelin 1, which is probably identical to rat leukocyte granulin, exhibits proliferative and antiproliferative effects on epithelial cells in vitro.

Role of protein kinase C in IFN-mediated Ly-6E antigen induction.

The YAC T cell lymphoma normally does not express Ly-6E mRNA or Ly-6E surface molecules but can be induced to do so on incubation with either IFN-gamma or IFN-alpha/beta. This system afforded a model to assess the possible role of protein kinase C (PKC) in IFN-mediated Ly-6E induction. First, we used various pharmacologic agents known to interfere with the function of PKC or other kinases.

Analysis of three distinct Ly6-A-related cDNA sequences isolated from rat kidney.

Mouse Ly6A and Ly6C cDNA probes were hybridized to total RNA of rat tissues and, as in mouse, the highest level of Ly6-related transcripts was detected in kidney. Therefore, Ly6-related cDNA clones were isolated from a commercial rat kidney cDNA library in lambda gt11. Four of these (RK3, RK6, RK10, and RK11) have been fully characterized, and represent transcripts from three distinct genes.

The CD59 antigen is a structural homologue of murine Ly-6 antigens but lacks interferon inducibility.

A cDNA encoding the human leukocyte antigen CD59 has been isolated from the erythroid cell line K-562 and its identity confirmed through expression in COS cells. Northern blotting reveals three message species of approximately 800, 1400 and 2000 bases in size, which are constitutively expressed in all lymphoid, erythroid, myeloid, and neural cell types tested thus far. Southern blotting of human DNA indicates a pattern consistent with the presence of a single gene, which has been mapped to chromosome 11 by somatic cell hybrids.

Kinetic analysis of Ly-6 gene induction in a T lymphoma by interferons and interleukin 1, and demonstration of Ly-6 inducibility in diverse cell types.

The Ly-6 locus contains multiple genes encoding cell surface proteins, two of which, when cross-linked by antibodies, effect antigen-independent activation of T lymphocytes. In this study, cDNA for Ly-6-encoded antigens have been used as probes to examine RNA from various tissues and transformed cell lines for constitutive levels of Ly-6 RNA expression. Analyses of RNA prepared from several different tissues revealed a high level of expression of Ly-6 RNA in kidney, spleen, heart and thymus, with a more moderate level of expression in liver, brain and lung tissue cells.

The T-cell activating protein (TAP) is up-regulated by endogenous IFN-gamma in activated T cells.

The surface expression of the T-cell activating protein (TAP) glycoprotein has been shown to be increased following mitogenic stimulation of T cells. Recently, we found that TAP is also augmented by exogenous interferon-gamma (IFN-gamma) in resting T cells. Because T cells are known to secrete IFN-gamma upon activation, we postulated that TAP enhancement in activated T cells may reflect an autocrine action of endogenous IFN-gamma.

Ly-6 A/E antigen of murine T cells is associated with a distinct pathway of activation. Requirements for interferon and exogenous interleukin 2.

The Ly-6 pathway of T cell activation was analyzed to identify its essential requirements. Using a monospecific chicken antiserum to Ly-6E, fully cross-reactive to its allelic counterpart, Ly-6A, but unreactive with other members of the Ly-6 family, we have found that interferon (IFN)-alpha/beta or gamma, Ly-6 antibody and interleukin 2 (IL 2) act synergistically in inducing T cell proliferation. The action of IFN can be attributed to induction of Ly-6A/E antigen on T cells, as described previously, and this induction is transcriptionally controlled.

Mls and the helper T-cell repertoire. I. Mls as a regulator of T-helper cell activation.

We provide evidence that the Mls reaction involves a broad cross-section of the helper cell population. In addition to those cells reacting overtly to Mls stimulatory spleen cells, there is a second large population of helper cells that are affected by an Mls difference. This latent Mls effect is manifested by either synergy or antagonism in mitogen-mediated, Ia-dependent T-cell activation, depending on Mlsa or Mlsb phenotypes of stimulator cells, respectively.

N-terminal and cDNA characterization of murine lymphocyte antigen Ly-6C.2.

The Ly-6C.2 molecule was purified from K36 tumor cells by affinity chromatography and gel filtration. The electrophoretically homogeneous preparation, with m.

Demonstration of phosphatidylinositol anchors on Ly-6 molecules by specific phospholipase C digestion and gel electrophoresis in octylglucoside.

Release by phosphatidylinositol-specific phospholipase C is frequently provided as evidence for membrane anchorage of a protein through phosphatidylinositol. Demonstration that the enzyme removes a lipophilic moiety from the protein is stronger evidence, and is presented here for members of the Ly-6 family of lymphocyte antigens: Ly-6A, C and E. Treatment of these molecules with the enzyme greatly increased their electrophoretic mobilities on polyacrylamide gels containing nonionic detergent.

Selective up-regulation by interferon-gamma of surface molecules of the Ly-6 complex in resting T cells: the Ly-6A/E and TAP antigens are preferentially enhanced.

Surface molecules encoded by the murine Ly-6 locus can transduce triggering signals in T cells and thus may play important roles in T cell function. Previously, we found that Ly-6 molecules are up-regulated by interferon (IFN)-alpha/beta in resting T cells. Here, we examined the possible influence of IFN-gamma on these molecules.