Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The vast mucosal interface separating external from internal compartments of the lung is under the surveillance of a population of blood-borne, bone marrow-derived dendritic cells (DC) characterized by constant turnover. Because these sentinel cells process foreign antigens that have penetrated the epithelial barrier and transport them to local lymph nodes, they require continuous replenishment by blood-borne cells. In the present study, the phenotype and function of DC and their precursors isolated from the vascular compartment of the lung were examined and compared with those in vena cava blood. Intravascular leukocytes were retrieved by exhaustive perfusion of the lung vasculature. Leukocytes harvested from the subdiaphragmatic vena cava of the same animal served as a source of DC in prepulmonary blood. Typical, large, major histocompatibility class II+ antigen (MHC II+) DC constituted < 1% of leukocytes from either vascular compartment. These cells expressed intercellular adhesion molecule [ICAM]-1 and lymphocyte function-associated antigen [LFA]-1 and many were ED1(+) (lysosomal antigen in monocytes, macrophages, and some DC). No ED2(+) cells (macrophages) were identified. Very few of the circulating DC expressed the alpha-like subunit of integrin recognized by the OX62 monoclonal antibody. A striking difference appeared when neutrophil-depleted leukocytes were cultured with granulocyte macrophage colony-stimulating factor (GM-CSF) for 3 d; the number of MHC II+ DC generated from pulmonary vascular leukocytes was 76% greater than that from the vena cava population. After pulse-labeling with tritiated thymidine ([3H]TdR) followed by 3 d of culture with GM-CSF, DC from either source remained virtually unlabeled, as determined by autoradiography. On the day of harvest, DC and their precursors obtained from either vascular compartment were poor stimulators of the mixed leukocyte reaction and required GM-CSF for development of their full accessory cell capability. These data suggest that, relative to leukocytes in vena cava blood, those in the lung vascular compartment are enriched in a population of mononuclear cells that are capable of differentiating into MHC II+ DC when exposed to the appropriate growth factors, including GM-CSF. This enriched population of DC precursors could represent a source from which lung DC may be readily recruited not only to replenish the normally turning-over mucosal DC, but also to participate in inflammatory reactions occurring in the lung.
Am J Respir Cell Mol Biol 1998 Nov
PMID:Dendritic cell precursors are enriched in the vascular compartment of the lung. 980 37

We investigated the in vitro effects of both prothymosin alpha1 (Pro alpha1) and transforming growth factor-beta1 (TGF-beta1) on the adhesion of peripheral blood lymphocytes (PBL) and on the expression of the adhesion molecules, endothelial-leukocyte adhesion molecule-1 (ELAM-1), intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on human umbilical vein endothelial cells (HUVECs). TGF-beta1 moderately but significantly decreased PBL-binding to interleukin-1 (IL-1)- stimulated HUVECs. However, Pro alpha1 in combination with TGF-beta1 completely restored the TGF-beta1 mediated effects. Other thymic peptides tested were ineffective. On HUVECs, TGF-beta1 diminished ICAM-1 and VCAM-1 expression, leaving ELAM-1 unchanged. Pro alpha1 in combination with TGF-beta1 showed no significant effects on ELAM-1 expression, but antagonized the TGF-beta1-induced decrease of ICAM-1 and VCAM-1 expression on activated HUVECs.
Int J Mol Med 1998 Apr
PMID:Prothymosin alpha1 antagonizes the inhibitory effects of transforming growth factor-beta1 on the adhesion of peripheral blood lymphocytes to human umbilical vein endothelial cells. 985 91

Human CD46 was identified as a complement regulator and was later shown to be a measles virus receptor. The ubiquitous distribution profile of CD46 accounted for systemic measles infection and general protection of host tissue/organs from autologous complement. A similar ubiquitous distribution was observed for swine and simian CD46 homologues based upon subsequent cDNA cloning and Northern analysis, reinforcing the roles of CD46. In contrast, recent cDNA cloning and distribution analyses of murine and guinea-pig CD46 revealed the predominant expression of these rodent CD46 homologues in the testis, especially in mature testicular germ cells. These results do not support the established functions of human CD46 but support the hypothesis that CD46 on sperm serves as a fertilization-related adhesion molecule toward eggs. Here, we review the structure, function and distribution of human CD46 and discuss the possible differences between human CD46 and its homologues recently cloned from a variety of non-human primates and other animals.
Int J Mol Med 1998 May
PMID:CD46 (membrane cofactor protein of complement, measles virus receptor): structural and functional divergence among species (review). 985

The relationship between the immune and the endometrial systems has been recently suggested to be critical to the development of endometriosis. We previously showed that one of the molecules involved in the complex events that allow this interaction is the adhesion molecule intercellular adhesion molecule (ICAM)-1. This study was designed to evaluate whether differences in ICAM-1 mRNA and protein expression might exist between eutopic endometrial cells and ectopic cells derived from endometriomas. Stromal cells were dispersed from samples of endometrium and ovarian endometriomas biopsied synchronously from 24 patients with endometriosis. We established that the relative expression of ICAM transcript was significantly higher in ectopic cells than that found in cultures derived from endometrial samples. Moreover, ectopic cells demonstrated a significant overexpression of ICAM-1 protein in both its cell-bound and soluble form (sICAM-1) (P < 0.05). Interestingly, endometrial secretion of sICAM-1 was shown to vary during the menstrual cycle as proliferative phase samples released significantly higher concentrations of the soluble protein compared to the secretory phase. In contrast, this cycle-dependent pattern was absent in stromal cells derived from endometriomas. Moreover, interleukin (IL-1beta) was able to increase sICAM-1 shedding from endometrial cells in a concentration-dependent manner and this IL-1beta-mediated induction could be slightly enhanced by oestradiol. As sICAM-1 is able to interfere with ICAM-1-mediated immune functions, the release of higher concentrations from ectopic samples may be the mechanism by which ectopic endometrial cells escape immunosurveillance.
Mol Hum Reprod 1998 Dec
PMID:Expression of intercellular adhesion molecule (ICAM)-1 mRNA and protein is enhanced in endometriosis versus endometrial stromal cells in culture. 987 66

Rat cardiac sarcolemmal Ca2+/Mg2+ ectoATPase (Myoglein), a membrane-bound enzyme requiring millimolar concentrations of Ca2+ or Mg2+ for maximal hydrolysis of ATP, has been purified to apparent homogeneity. Tryptic digestion and amino acid sequencing was used to design an oligonucleotide probe for screening a rat heart cDNA library; this produced a partial cDNA clone (pND2.1), and sequencing of a 400 base pair portion revealed a 100% homology to human platelet CD36. Northern blotting with pND2.1 detected a 3.1 kb transcript in rat heart but not in other tissues. Interspecies expression analysis (cardiac tissue total RNA blot probed with pND2.1) detected a approximately 2.0 kb transcript in canine, rabbit and porcine heart, whereas transcripts of a 4.1 kb, approximately 3.0 kb and 2.1 kb were observed in human cardiac tissue. A rat genomic DNA Southern blot, probed with pND2.1, indicated that there was a single copy of the gene in the rat genome. Expression of the pND2.1 cDNA in E. coli produced an 89 kDa polypeptide recognized by anti-human CD36 antibody but not by anti-rat Ca2+/Mg2+ ectoATPase antibody. It is concluded that rat cardiac Ca2+/Mg2+ ectoATPase is tightly associated with a protein highly homologous to the adhesion molecule CD36.
J Mol Cell Cardiol 1998 Nov
PMID:Molecular cloning of rat cardiac sarcolemmal Ca2+/Mg2+ ectoATPase (Myoglein). 992 63

The intense inflammatory reaction following reperfusion of the infarcted myocardium has been implicated as a factor in extension of injury. However, this inflammatory reaction is also critical to tissue repair. The cellular responses that mediate these functions are orchestrated by sequential induction and/or release of cytokines resulting in a closely regulated cytokine cascade. This paper reviews research on these cytokine cascades, their cellular origin, and factors which control the cellular response to their presence. Factors examined include leukotaxis, phenotypic transition of leukocytes, adhesion molecule induction and the role of cytokines in tissue repair and scar formation.
J Mol Cell Cardiol 1998 Dec
PMID:Cytokines and the microcirculation in ischemia and reperfusion. 999 May 29

The adult avian forebrain continues to generate neurons from ventricular zone (VZ) precursor cells, whose neuronal progeny then migrate into the brain parenchyma. Migrating neurons respond to the Ig-family adhesion molecule NgCAM with increments in cytosolic calcium, and migration is disrupted by anti-NgCAM Ig. The calcium response to NgCAM is developmentally restricted to bipolar migrants during a period spanning 6 to 9 DIV. This period corresponds to the postmitotic age at which new neurons leave the adult VZ to traverse a subjacent layer of estrogen-receptive "gatekeeper" neurons. Since neuronal passage through this layer occurs concurrently with the onset of NgCAM-dependent calcium signaling, we asked whether acquisition of the calcium response to NgCAM required estrogen exposure. Among neurons arising from explants of the adult finch neostriatal VZ, only those supplemented with estrogen developed calcium responses to NgCAM; neither explants raised in the absence of estrogen, nor those supplemented with testosterone, did so. Neurons in all three groups expressed NgCAM, had equivalent baseline calcium levels, and responded identically to K+-depolarization. Nonetheless, many more neurons migrated from explants of both finch and canary VZ raised in estrogen-supplemented media than from their estrogen-deprived counterparts, even though no effect of estrogen on neuronal survival per se was noted. These findings suggest that estrogen encourages the initial departure and assumption of signal competence by neurons arising from the adult avian VZ, thereby promoting their parenchymal recruitment and migration success.
Mol Cell Neurosci 1999 Jan
PMID:Estrogen promotes the initial migration and inception of NgCAM-dependent calcium-signaling by new neurons of the adult songbird brain. 1004 30

The purpose of this study was to localize intercellular adhesion molecule (ICAM)-1 and ICAM-2 in human endometrium and myometrium throughout the menstrual cycle, and to determine whether the expression of these molecules is regulated by interferon (IFN)-gamma. ICAM-1 and ICAM-2 distribution was examined in endometrial biopsies by immunocytochemistry, and Northern blotting was used to quantify ICAM-1 and ICAM-2 mRNA expression in isolated endometrial glands. Stromal fibroblast cultures were exposed to IFN-gamma and the effect on expression of ICAM-1 and ICAM-2 was determined by immunocytochemistry and Northern blotting. ICAM-1 was localized in vivo to the apical surface of the glandular epithelium, the vascular endothelium and endometrial stromal cells throughout the menstrual cycle. Stromal expression of ICAM-1 was up-regulated in menstrual specimens. Northern blotting confirmed the presence of ICAM-1 mRNA in isolated endometrial glands. The expression of ICAM-1 antigen and message was increased in stromal cell culture after incubation with IFN-gamma in a time-dependent manner, suggesting that this cytokine stimulates the expression of ICAM-1 in the endometrial stroma. ICAM-2 antigen expression was restricted to the vascular endothelium. ICAM-2 mRNA was absent in endometrial glands. The widespread distribution of ICAM-1 in human endometrium suggests that this molecule is involved in the process of menstruation, the functioning of glands, blood vessels and stroma, and in regulating leukocyte trafficking into the tissue. ICAM-2 is restricted to the vascular endothelium where it might modulate leukocyte invasion of the stroma and myometrial connective tissue.
Mol Hum Reprod 1999 Jan
PMID:Expression of intercellular adhesion molecules ICAM-1 and ICAM-2 in human endometrium: regulation by interferon-gamma. 1005 Jun 64

We tested the hypothesis that activation of protein kinase C (PKC) and generation of oxidants are critical sequential signals mediating tumor necrosis factor (TNF)-alpha-induced activation of nuclear factor-kappaB (NF-kappaB) and transcription of the intercellular adhesion molecule (ICAM)-1 gene. Stimulation of human pulmonary artery endothelial (HPAE) cells with TNF-alpha (100 U/ml) induced the activation of PKC and, subsequently, generation of oxidants. Pretreatment with calphostin C, a specific PKC inhibitor, prevented oxidant generation after TNF-alpha stimulation, indicating that PKC activation mediated the production of oxidants in HPAE cells. In contrast, pretreatment of HPAE cells with N-acetylcysteine, an antioxidant and a precursor of glutathione, failed to prevent PKC activation, indicating that PKC activation was not secondary to the oxidant production. These findings suggest that oxidant generation in endothelial cells occurs downstream of PKC activation. However, both PKC activation and oxidant generation were necessary for ICAM-1 mRNA expression because the pretreatment of HPAE cells with either calphostin C or N-acetylcysteine inhibited the TNF-alpha-induced activation of NF-kappaB and prevented the activation of ICAM-1 promoter. Prolonged exposure of HPAE cells to the phorbol ester, phorbol-12-myristate-13-acetate, which is known to deplete all except atypical PKC isozymes, failed to prevent TNF-alpha-induced ICAM-1 mRNA expression. We conclude that TNF-alpha-induced oxidant generation secondary to the activation of a phorbol ester-insensitive PKC isozyme signals the activation NF-kappaB and ICAM-1 gene transcription.
Mol Pharmacol 1999 Mar
PMID:Protein kinase C-activated oxidant generation in endothelial cells signals intercellular adhesion molecule-1 gene transcription. 1005 43

The nontransmembrane protein tyrosine phosphatase SHP-2 plays a critical role in growth factor and cytokine signaling pathways. Previous studies revealed that a fraction of SHP-2 moves to focal contacts upon integrin engagement and that SHP-2 binds to SHP substrate 1 (SHPS-1)/SIRP-1alpha, a transmembrane glycoprotein with adhesion molecule characteristics (Y. Fujioka et al., Mol. Cell. Biol. 16:6887-6899, 1996; M. Tsuda et al., J. Biol. Chem. 273:13223-13229). Therefore, we asked whether SHP2-SHPS-1 complexes participate in integrin signaling. SHPS-1 tyrosyl phosphorylation increased upon plating of murine fibroblasts onto specific extracellular matrices. Both in vitro and in vivo studies indicate that SHPS-1 tyrosyl phosphorylation is catalyzed by Src family protein tyrosine kinases (PTKs). Overexpression of SHPS-1 in 293 cells potentiated integrin-induced mitogen-activated protein kinase (MAPK) activation, and potentiation required functional SHP-2. To further explore the role of SHP-2 in integrin signaling, we analyzed the responses of SHP-2 exon 3(-/-) and wild-type cell lines to being plated on fibronectin. Integrin-induced activation of Src family PTKs, tyrosyl phosphorylation of several focal adhesion proteins, MAPK activation, and the ability to spread on fibronectin were defective in SHP-2 mutant fibroblasts but were restored upon SHP-2 expression. Our data suggest a positive-feedback model in which, upon integrin engagement, basal levels of c-Src activity catalyze the tyrosyl phosphorylation of SHPS-1, thereby recruiting SHP-2 to the plasma membrane, where, perhaps by further activating Src PTKs, SHP-2 transduces positive signals for downstream events such as MAPK activation and cell shape changes.
Mol Cell Biol 1999 Apr
PMID:Regulation of early events in integrin signaling by protein tyrosine phosphatase SHP-2. 1008 87


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>