Subset of DC-SIGN(+) dendritic cells in human blood transmits HIV-1 to T lymphocytes.

The dendritic cell (DC)-specific molecule DC-SIGN is a receptor for the HIV-1 envelope glycoprotein gp120 and is essential for the dissemination of HIV-1. DC-SIGN is expressed by DCs, both monocyte-derived DCs and DCs in several tissues, including mucosa and lymph nodes. To identify a DC-SIGN(+) DC in blood that may be involved in HIV-1 infection through blood, we have analyzed the expression of DC-SIGN in human blood cells.

The dendritic cell-specific adhesion receptor DC-SIGN internalizes antigen for presentation to T cells.

Dendritic cells (DCs) capture Ags or viruses in peripheral tissue to transport them to lymphoid organs to induce cellular T cell responses. Recently, a DC-specific C-type lectin was identified, DC-specific ICAM-grabbing non-integrin (DC-SIGN), that functions as cell adhesion receptor mediating both DC migration and T cell activation. DC-SIGN also functions as an HIV-1R that captures HIVgp120 and facilitates DC-induced HIV transmission of T cells.

Identification of different binding sites in the dendritic cell-specific receptor DC-SIGN for intercellular adhesion molecule 3 and HIV-1.

The novel dendritic cell (DC)-specific human immunodeficiency virus type 1 (HIV-1) receptor DC-SIGN plays a key role in the dissemination of HIV-1 by DC. DC-SIGN is thought to capture HIV-1 at mucosal sites of entry, facilitating transport to lymphoid tissues, where DC-SIGN efficiently transmits HIV-1 to T cells. DC-SIGN is also important in the initiation of immune responses by regulating DC-T cell interactions through intercellular adhesion molecule 3 (ICAM-3).

Rhesus macaque and chimpanzee DC-SIGN act as HIV/SIV gp120 trans-receptors, similar to human DC-SIGN.

Dendritic cells (DC) have been implicated in the pathogenesis of both human and simian immunodeficiency viruses (HIV and SIV, respectively). The DC-specific HIV-1 trans-receptor DC-SIGN is thought to be essential for viral dissemination by DC. Abundant expression in lymphoid tissues also implies a function for DC-SIGN in chronic HIV-1 infections, in facilitating persistent infection of T cells.

Analysis of integrin expression in U2OS cells cultured on various calcium phosphate ceramic substrates.

Earlier we observed that calcium phosphate (Ca-P)-coated implant substrates stimulated the differentiation of osteoblast-like cells compared to uncoated substrates. This suggests that this difference in osteogenic induction is due to the chemical composition of the substratum. We hypothesized that Ca-P coatings modulate integrin expression patterns, because those receptors are the sensors of the cell.

DC-SIGN, a dentritic cell-specific HIV-1 receptor present in placenta that infects T cells in trans-a review.

Dendritic cells (DC) capture micro-organisms that enter peripheral mucosal tissues and then migrate to secondary lymphoid organs, where they present in antigenic form to resting T cells and thus initiate adaptive immune responses. Here we describe the properties of a DC-specific C-type lectin, DC-SIGN, that is highly expressed on DC present in mucosal tissues and binds to the HIV-1 envelope glycoprotein gp120. DC-SIGN does not function as a receptor for viral entry into DC, but instead promotes efficient infection in trans of cells that express CD4 and chemokine receptors.

DC-SIGN-ICAM-2 interaction mediates dendritic cell trafficking.

Dendritic cells (DCs) are recruited from blood into tissues to patrol for foreign antigens. After antigen uptake and processing, DCs migrate to the secondary lymphoid organs to initiate immune responses. We now show that DC-SIGN, a DC-specific C-type lectin, supports tethering and rolling of DC-SIGN-positive cells on the vascular ligand ICAM-2 under shear flow, a prerequisite for emigration from blood.

A dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)-related protein is highly expressed on human liver sinusoidal endothelial cells and promotes HIV-1 infection.

The discovery of dendritic cell (DC)-specific intercellular adhesion molecule (ICAM)-3-grabbing nonintegrin (DC-SIGN) as a DC-specific ICAM-3 binding receptor that enhances HIV-1 infection of T cells in trans has indicated a potentially important role for adhesion molecules in AIDS pathogenesis. A related molecule called DC-SIGNR exhibits 77% amino acid sequence identity with DC-SIGN. The DC-SIGN and DC-SIGNR genes map within a 30-kb region on chromosome 19p13.

A single amino acid in the cytoplasmic domain of the beta 2 integrin lymphocyte function-associated antigen-1 regulates avidity-dependent inside-out signaling.

The leukocyte-specific beta(2) integrin lymphocyte function-associated antigen-1 (LFA-1) (alpha(L)/beta(2)) mediates activation-dependent adhesion to intercellular adhesion molecule (ICAM)-1. In leukocytes, LFA-1 requires activation by intracellular messengers to bind ICAM-1. We observed malfunctioning of LFA-1 activation in leukemic T cells and K562-transfected cells.

The LFA-1 integrin supports rolling adhesions on ICAM-1 under physiological shear flow in a permissive cellular environment.

The LFA-1 integrin is crucial for the firm adhesion of circulating leukocytes to ICAM-1-expressing endothelial cells. In the present study, we demonstrate that LFA-1 can arrest unstimulated PBL subsets and lymphoblastoid Jurkat cells on immobilized ICAM-1 under subphysiological shear flow and mediate firm adhesion to ICAM-1 after short static contact. However, LFA-1 expressed in K562 cells failed to support firm adhesion to ICAM-1 but instead mediated K562 cell rolling on the endothelial ligand under physiological shear stress.

DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells.

Dendritic cells (DC) capture microorganisms that enter peripheral mucosal tissues and then migrate to secondary lymphoid organs, where they present these in antigenic form to resting T cells and thus initiate adaptive immune responses. Here, we describe the properties of a DC-specific C-type lectin, DC-SIGN, that is highly expressed on DC present in mucosal tissues and binds to the HIV-1 envelope glycoprotein gp120. DC-SIGN does not function as a receptor for viral entry into DC but instead promotes efficient infection in trans of cells that express CD4 and chemokine receptors.

Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses.

Contact between dendritic cells (DC) and resting T cells is essential to initiate a primary immune response. Here, we demonstrate that ICAM-3 expressed by resting T cells is important in this first contact with DC. We discovered that instead of the common ICAM-3 receptors LFA-1 and alphaDbeta2, a novel DC-specific C-type lectin, DC-SIGN, binds ICAM-3 with high affinity.

Low-affinity LFA-1/ICAM-3 interactions augment LFA-1/ICAM-1-mediated T cell adhesion and signaling by redistribution of LFA-1.

Although ICAM-3 is implicated in both adhesion and signal transduction events of leukocytes, its low affinity for LFA-1 compared to other ligands of LFA-1 has puzzled many investigators. Here we investigated the role of ICAM-3 in supporting LFA-1-mediated ICAM-1 binding and subsequently cell signaling. We observed that although ICAM-3 binds poorly to LFA-1 expressed on resting T cells, it specifically facilitates and increases LFA-1-mediated adhesion to the high affinity ligand of LFA-1, ICAM-1.

The actin cytoskeleton regulates LFA-1 ligand binding through avidity rather than affinity changes.

To elucidate the role of the cytoskeleton regulating avidity or affinity changes in the leukocyte adhesion receptor lymphocyte function-associated antigen-1 (LFA-1) (alpha(L)beta(2)), we generated mutant cytoplasmic LFA-1 receptors and expressed these into the erythroleukemic cell line K562. We determined whether intercellular adhesion molecule-1 (ICAM-1)-mediated adhesion of LFA-1, lacking parts of its cytoplasmic tails, is regulated through receptor diffusion/clustering and/or by altered ligand binding affinity. All cytoplasmic deletion mutants that lack the complete beta(2) cytoplasmic tail and/or the conserved KVGFFKR sequence in the alpha(L) cytoplasmic tail were constitutively active and expressed high levels of the activation epitopes NKI-L16 and M24.

3D single-particle tracking and optical trap measurements on adhesion proteins.

A three-dimensional single-particle tracking system was combined with an optical trap to investigate the behavior of transmembrane adhesion proteins. We exploited this setup to investigate which part of the cell adhesion protein LFA-1 forms a connection to the cytoskeleton after binding to its ligand ICAM-1. LFA-1 is an integrin consisting of an alpha and a beta chain.

High frequency of adhesion defects in B-lineage acute lymphoblastic leukemia.

Aberrant proliferation, differentiation, and/or migration of progenitors observed in various hematological malignancies may be caused by defects in expression and/or function of integrins. In this study, we have developed a new fluorescent beads adhesion assay that facilitates flow cytometric investigation of lymphocyte function-associated antigen 1 (LFA-1)- and very late activation antigen-4 (VLA-4)-mediated functional adhesion in B-lineage acute lymphoblastic leukemia (ALL) of both the CD10(-) and CD10(+) (leukemic) cell population within one blood or bone marrow sample. Surprisingly, of the 20 B-lineage ALL patients investigated, 17 contained a leukemic cell population with LFA-1- and/or VLA-4-mediated adhesion defects.

Preventing NIDDM among aboriginal people: is exercise the answer? Description of a pilot project using exercise to prevent gestational diabetes.

Rates of diabetes and its complications have reached epidemic proportions among North American Aboriginal peoples. This appears largely due to changes in diet and activity levels associated with a shift away from traditional lifestyles. Since exercise has been shown to be effective in preventing non-insulin-dependent diabetes mellitus (NIDDM), Aboriginal communities may be able to reduce their rates of the disease by incorporating exercise programs into their public health programs.

Cytoplasmic tails of beta 1, beta 2, and beta 7 integrins differentially regulate LFA-1 function in K562 cells.

The beta 2 integrin lymphocyte function-associated antigen 1 (LFA-1) mediates activation-dependent adhesion of lymphocytes. To investigate whether lymphocyte-specific elements are essential for LFA-1 function, we expressed LFA-1 in the erythroleukemic cell line K562, which expresses only the integrin very late antigen 5. We observed that LFA-1-expressing K562 cannot bind to intercellular adhesion molecule 1-coated surfaces when stimulated by phorbol 12-myristate 13-acetate (PMA), whereas the LFA-1-activating antibody KIM185 markedly enhanced adhesion.

Dual role of the actin cytoskeleton in regulating cell adhesion mediated by the integrin lymphocyte function-associated molecule-1.

Intracellular signals are required to activate the leukocyte-specific adhesion receptor lymphocyte function-associated molecule-1 (LFA-1; CD11a/CD18) to bind its ligand, intracellular adhesion molecule-1 (ICAM-1). In this study, we investigated the role of the cytoskeleton in LFA-1 activation and demonstrate that filamentous actin (F-actin) can both enhance and inhibit LFA-1-mediated adhesion, depending on the distribution of LFA-1 on the cell surface. We observed that LFA-1 is already clustered on the cell surface of interleukin-2/phytohemagglutinin-activated lymphocytes.

Clinical characteristics and management of diabetic patients residing in a nursing home.

In 38 diabetic patients, admitted on a long-term basis to a nursing home, the clinical situation and presence of secondary diabetic complications were assessed, and their macrovascular complications and degree of glycemic control compared with those in ambulatory diabetic patients, matched for age, sex, known duration of diabetes and specific antidiabetic therapy. No differences in blood glucose control, plasma triglycerides, blood pressure and serum creatinine were observed between both groups of patients. Plasma cholesterol levels were higher in the ambulatory patients (6.

Stimulation of glucagon secretion by gastric inhibitory polypeptide in patients with hepatic cirrhosis and hyperglucagonemia.

Porcine gastric inhibitory polypeptide (GIP) was infused iv (120 micrograms in 60 min) in seven patients with biopsy-proven hepatic cirrhosis who had surgical porta-caval anastomoses and hyperglucagonemia in the postabsorptive state. The infusions resulted in elevation of blood levels of immunoreactive GIP into the upper range of those observed after ingestion of large mixed meals. This was accompanied by significant increments in immunoreactive glucagon (IRG) in the plasma.

Hyperglucagonemia in liver cirrhosis with portal-systemic venous anastomoses: responses of plasma glucagon and gastric inhibitory polypeptide to oral or intravenous glucose in cirrhotics with normal or elevated fasting plasma glucose levels.

Plasma immunoreactive glucagon (IRG) was examined in volunteers with biopsy-proven cirrhosis of the liver after recovery from surgical portal--caval anastomosis. A wide range of increased total plasma IRG concentrations was found after overnight fast in groups of cirrhotic subjects with and without fasting hyperglycemia. Gel filtration chromatography of plasma showed a major component in the 3500-mol wt fraction in all cases so studied.

Prolactin-secreting tumors and hypogonadism in 22 men.

We studied 22 men with prolactin-secreting pituitary tumors and hypogonadism. Twenty complained of impotence, nine had visual impairment, and three experienced galactorrhea. None of the 17 patients undergoing operation or radiotherapy, or both, were subsequently normoprolactinemic.