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PubMed1997

Moloney murine leukemia virus long terminal repeat activates monocyte chemotactic protein-1 protein expression and chemotactic activity.

Moloney murine leukemia virus (Mo-MuLV) is a thymotropic and leukemogenic retrovirus which causes T lymphomas. Recently, Mo-MuLV has been shown to trans-activate cellular genes. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine which can promote the migration and diapedesis of monocytes and lymphocytes, as well as inducing metastasis of lymphomas. Here we demonstrate that introduction of Mo-MuLV or the MuLV LTR alone, transiently or stably, into Balb/c-3T3 cells or HeLa cells resulted in 9-11 fold increases in MCP-1 transcripts. This trans-activation of the MCP-1 gene by the Mo-MuLV LTR is independent of the physical location of the MCP-1 gene or of the LTR, occurring whether the LTR or the MCP-1 gene is integrated in the genome or transiently expressed. Immunoblot analysis using an anti-MCP-1 polyclonal antibody showed that the expression of the MuLV LTR in HeLa cells also induced the appearance of the MCP-1 protein. Boyden Chamber analysis demonstrated that the MCP-1 chemotactic activity produced by HeLa cells with an integrated MuLV LTR was elevated by 11 fold and that neutralizing antibody to human MCP-1 abrogated monocyte migration in response to MuLV LTR expression. Promoter deletional analysis showed the LTR responsive cis-acting element in the MCP-1 promoter is located between -141 and -88. Deletion of this region abolished the trans-activation of MCP-1 by the LTR. These LTR-mediated activations of a chemotactic and inflammatory cytokine may be relevant as mechanisms whereby retroviruses which do not contain oncogenes can induce neoplasia.

Animals↗
PubMed1976

Effects of egg factors on cyclic nucleotide metabolism in sea urchin sperm.

Cyclic AMP in Strongylocentrotus purpuratus sperm was elevated approximately 2-fold by theophylline or 1-methyl-3-isobutylxanthine. Factors released from sea urchin eggs (FRE) elevated sperm cyclic AMP by about 7-fold within 1 min, and the combination of FRE with theophylline increased sperm cyclic AMP up to 100-fold within 1 min. Cyclic GMP in sea urchin sperm was slightly elevated by theophylline, but was lowered by FRE. Cyclic GMP in sperm treated with FRE plus theophylline was not higher than in sperm treated with theophylline alone. The ability of FRE-containing sea water to increase sperm cyclic AMP in the presence of theophylline was altered only slightly if at all by boiling, but it was decreased by about 50% by dialysis and destroyed by ashing. Filtration of FRE on Sephadex G-50 columns yielded two peaks of cyclic AMP-elevating activity. One peak (peak I) was eluted at the column void volume, and the other (peak II) was retained by the column. The cyclic GMP-lowering activity was located in fractions approximately corresponding to peak I of cyclic AMP-elevating activity. Dialysis of FRE-containing sea water before its application to the G-50 column virtually eliminated peak II of the cyclic AMP-elevating activity. When the cyclic AMP-elevating activity in peak I was filtered on Bio Gel A-5m columns, it also migrated at or near the column void volume. Fractions corresponding to peak I contained material that inhibited both guanylate and adenylate cyclase activities in broken cell preparations of sperm and guanylate cyclase from rat lung. The inhibitory material was stable to boiling, non-dialyzable, and destroyed by ashing. Under a variety of conditions, FRE-containing sea water or cyclic AMP-elevating peaks I or II did not stimulate sperm adenylate cyclase activity in broken cell preparations.

Adenylyl Cyclases↗
PubMed1986

Immunopotentiating activities of cell walls, peptidoglycans, and teichoic acids from two strains of Listeria monocytogenes.

Crude cell wall (CCW), enzyme purified wall (PF), peptidoglycans (PEP), and teichoic acid fractions from two strains of Listeria monocytogenes (EGD and a human isolate) were analyzed by electron microscopy, chemical analyses, and various immunological assays. Electron microscopy and chemical analyses revealed that both strains were quite similar. The CCW, PF, and PEP fractions were mitogenic for mouse lymphocytes, could activate macrophages in vivo but not in vitro, and stimulated nonspecific immunity in vivo to Candida albicans. The PF and PEP fractions but not the CCW induced migration inhibition factor production. The CCW and PEP fractions were tested and found to elevate natural killer activity in vivo. Teichoic acid fractions had no activity in the above assays. Since most of the immunological activities were retained in the PEP fraction, we examined this fraction to determine the kinetics of the mitogenic response and the nature of the responding cell population. The peak mitogenic response occurred on day 2 over a 6-day period. This response was not enriched in T-cell-enriched populations but followed the pattern of LPS in B-cell-enriched populations.

Adjuvants, Immunologic↗
PubMed2006

Beta thalassemia IVS-I-5(G-->C) heterozygosity masked by the presence of HbJ-Meerut in a Dutch-Indian patient.

We describe the genotype/phenotype correlation in a 35 year old anemic female referred to our laboratory because a fast eluting minor fraction on HPLC, mild hemolysis and hematological parameters suggesting a Thalassemia trait, eventually in combination with iron depletion. Direct sequencing of the alpha globin genes revealed heterozygosity for HbJ-Meerut, a Glu-->Ala substitution at residue 120 not justifying the hematological parameters. No other point mutations were found on the alpha genes and Gap-PCR excluded the 6 common deletion defects. Direct sequencing of the beta-globin genes revealed the IVS-I-5 (G-->C) transversion in absence of the elevated HbA2 levels usually measured in carriers of this beta-Thalassemia mutation. The HbA2 tetramer in the presence of HbJ-Meerut divides in two parts. One alphaN2/delta2 migrating on the right spot on HPLC. The other alphaJ2/delta2 migrating under the HbA fraction. Classic alkaline electrophoresis and the modern capillary electrophoresis CE showed these two tetramers and the reduction of the elevated HbA2 level of the beta-Thalassemia trait by at least 20% due to HbA2 Meerut.

Adult↗
PubMed2005

Intravital observation of Plasmodium berghei sporozoite infection of the liver.

Plasmodium sporozoite invasion of liver cells has been an extremely elusive event to study. In the prevailing model, sporozoites enter the liver by passing through Kupffer cells, but this model was based solely on incidental observations in fixed specimens and on biochemical and physiological data. To obtain direct information on the dynamics of sporozoite infection of the liver, we infected live mice with red or green fluorescent Plasmodium berghei sporozoites and monitored their behavior using intravital microscopy. Digital recordings show that sporozoites entering a liver lobule abruptly adhere to the sinusoidal cell layer, suggesting a high-affinity interaction. They glide along the sinusoid, with or against the bloodstream, to a Kupffer cell, and, by slowly pushing through a constriction, traverse across the space of Disse. Once inside the liver parenchyma, sporozoites move rapidly for many minutes, traversing several hepatocytes, until ultimately settling within a final one. Migration damage to hepatocytes was confirmed in liver sections, revealing clusters of necrotic hepatocytes adjacent to structurally intact, sporozoite-infected hepatocytes, and by elevated serum alanine aminotransferase activity. In summary, malaria sporozoites bind tightly to the sinusoidal cell layer, cross Kupffer cells, and leave behind a trail of dead hepatocytes when migrating to their final destination in the liver.

Aedes↗
PubMed1997

Intracellular precursor interleukin (IL)-1alpha, but not mature IL-1alpha, is able to regulate human endothelial cell migration in vitro.

The human umbilical vein endothelial cell (HUVEC) has a finite lifespan in vitro, and senescent HUVEC contain elevated levels of the negative growth regulator interleukin (IL)-1alpha. IL-1alpha is translated as a signal peptide sequence-less cytosolic 31-kDa precursor (IL-1alpha p), which undergoes proteolytic activation to release the mature carboxyl terminus 17-kDa protein (IL-1alpha m). Both the IL-1alpha p and IL-1alpha m proteins are biologically active as exogenous cytokines. Interestingly, only IL-1alpha p contains a nuclear localization sequence between residues 79 and 85. To further study the role of intracellular IL-1alpha in the regulation of human endothelial cell function, a spontaneous HUVEC transformant was stably transfected with IL-1alpha p, IL-1alpha m, and the IL-1alpha p K82N mutant, which attenuates the nuclear traffic of IL-1alpha p. Interestingly, the IL-1alpha p transfectants were found to have a lower migratory potential than either IL-1alpha m or IL-1alpha p K82N transfectants, and the addition of the IL-1 receptor antagonist did not alter the migration of these cells. Immunofluorescence microscopy demonstrated that only the IL-1alpha p transfectants exhibited prominent staining for beta-catenin-associated cell-to-cell contacts, as well as pronounced vimentin intermediate filaments and actin cytoskeleton staining. These data suggest that IL-1alpha p, and not IL-1alpha m, may function as an intracellular regulator of the migratory capacity of the human endothelial cell and that the nuclear localization sequence present within IL-1alpha p may be involved in regulating this function.

Cell Movement↗
PubMed2004

Stimulation of vascular smooth muscle cell proliferation and migration by apolipoprotein(a) is dependent on inhibition of transforming growth factor-beta activation and on the presence of kringle IV type 9.

Elevated plasma concentrations of lipoprotein(a) are a risk factor for the development of a variety of atherosclerotic disorders. Despite intensive study, the mechanisms by which lipoprotein(a) promotes these disorders remain to be unequivocally defined. It has been demonstrated that lipoprotein(a), through its unique constituent apolipoprotein(a) (apo(a)), stimulates vascular smooth muscle cell (SMC) migration and proliferation. These effects arise from the ability of apo(a) to inhibit the formation of active transforming growth factor beta (TGF-beta) from its latent precursor, which in turn is caused by the ability of apo(a) to decrease the formation of plasmin from its precursor plasminogen. We utilized a battery of recombinant apo(a) variants that represent systematic deletions of the various domains in the molecule to further probe the mechanism underlying the effect of apo(a) on SMC responses. All recombinant apo(a) variants that contained kringle IV type 9 were able to stimulate SMC proliferation and migration and to decrease the formation of active TGF-beta; conversely all recombinant apo(a) variants lacking kringle IV type 9 had no effect on these parameters. The kringle IV type 9-dependent effects of apo(a) on SMC proliferation required the presence of plasminogen, suggesting for the first time that this kringle mediates the ability of apo(a) to inhibit pericellular plasmin formation.

Apolipoproteins A↗
PubMed2000

The inflammatory reaction during venous hypertension in the rat.

OBJECTIVE: Numerous studies have examined arterial occlusion followed by reperfusion but few studies have reported about venular occlusion which, in contrast to arterial occlusion, is associated with elevation of the capillary blood pressure. Here we examine leukocytes infiltration and tissue injury in rat mesentery during local venular occlusion and venous hypertension followed by reperfusion, and determine the level of protection offered by pretreatment with micronized, purified flavonoid fraction (MPFF). METHODS: Leukocyte rolling, adhesion, migration, and parenchymal cell death as detected by propidium iodide labeling were determined during venular occlusion using a micropipette followed by reperfusion in the rat mesenteric microcirculation pretreated with 0, 50, or 100 mg/kg MPFF for 7 days. Spontaneous leukocyte activation by nitroblue tetrazolium reduction and expression of CD18 and CD62L on naive donor neutrophils incubated with plasma from each treatment group were determined. RESULTS: Venous occlusion led to elevated levels of leukocyte rolling, adhesion, and migration as well as parenchymal cell death. These injurious processes were significantly inhibited by MPFF in a those-dependent fashion. MPFF reduced spontaneous leukocyte NBT reduction and the neutropil expression of CD62L, even though CD18 was not affected. CONCLUSION: These results suggested that microvascular occlusion in venules with elevation of the micropressure followed by reperfusion is a highly cytotoxic process in the rat mesentery which can be attenuated by MPFF pretreatment.

Animals↗
PubMed2001

Hepatocyte growth factor/scatter factor stimulates migration of rat mammary fibroblasts through both mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt pathways.

Hepatocyte growth factor/scatter factor (HGF/SF) is considered to be a mesenchymal-derived factor that acts via a dual system receptor, consisting of the MET receptor and proteoglycans present on adjacent epithelial cells. Surprisingly, HGS/SF stimulated the migration of rat mammary (Rama) 27 fibroblasts, although it failed to stimulate their proliferation. HGF/SF stimulated a transient activation of mitogen-activated protein kinases p44 and p42 (p42/44(MAPK)), with a maximum level of dual phosphorylation of p42/44(MAPK) occurring 10-15 min after the addition of the growth factor, which was followed by a rapid decrease to near basal levels after 20 min. Interestingly, a second phase of p42/44(MAPK) dual phosphorylation was observed at later times (3 h to 10 h). PD098059, a specific inhibitor of MEK-1, prevented the dual phosphorylation of p42/44(MAPK) and also the phosphorylation of p90(RSK) (ribosomal subunit S6 kinase), which mirrored the kinetics of p42/44(MAPK) phosphorylation. Moreover, PD098059 prevented the HGF/SF-induced migration of Rama 27 cells. HGF/SF also induced an early increase in the phosphorylation of protein kinase B/Akt. Akt phosphorylation was elevated 15 min after the addition of HGF/SF and then declined to basal levels by 30 min. Wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PtdIns3K), prevented the increase in Akt phosphorylation and abolished HGF/SF-induced migration of fibroblasts. PD098059 also inhibited the stimulation of Akt phosphorylation by HGF/SF and wortmannin similarly inhibited the stimulation of p42/44(MAPK) dual phosphorylation. These results suggest that HGF/SF-induced motility depends on both the transient dual phosphorylation of p42/44(MAPK) and the activation of PtdIns3K in Rama 27 fibroblasts and that these pathways are mutually dependent.

Androstadienes↗
PubMed2006

The characteristics of tropospheric ozone seasonality observed from ozone soundings at Pohang, Korea.

This paper presents the first analysis of vertical ozone sounding measurements over Pohang, Korea. The main focus is to analyze the seasonal variation of vertical ozone profiles and determine the mechanisms controlling ozone seasonality. The maxima ozone at the surface and in the free troposphere are observed in May and June, respectively. In comparison with the ozone seasonality at Oki (near sea level) and Happo (altitude of 1840 m) in Japan, which are located at the same latitude as of Pohang, we have found that the time of the ozone maximum at the Japanese sites is always a month earlier than at Pohang. Analysis of the wind flow at the surface shows that the wind shifts from westerly to southerly in May over Japan, but in June over Pohang. However, this wind shift above boundary layer occurs a month later. This wind shift results in significantly smaller amounts of ozone because the southerly wind brings clean wet tropical air. It has been suggested that the spring ozone maximum in the lower troposphere is due to polluted air transported from China. However, an enhanced ozone amount over the free troposphere in June appears to have a different origin. A tongue-like structure in the time-height cross-section of ozone concentrations, which starts from the stratosphere and extends to the middle troposphere, suggests that the ozone enhancement occurs due to a gradual migration of ozone from the stratosphere. The high frequency of dry air with elevated ozone concentrations in the upper troposphere in June suggests that the air is transported from the stratosphere. HYSPLIT trajectory analysis supports the hypothesis that enhanced ozone in the free troposphere is not likely due to transport from sources of anthropogenic activity.

Atmosphere↗
PubMed1986

Variations in plasma corticosterone, estrone, estradiol-17 beta, and progesterone concentrations with forced renesting, molt, and body weight of captive female American kestrels.

Corticosterone, progesterone, estradiol-17 beta, and estrone were quantified in plasma collected weekly (April-September) from renesting and nonlaying female American kestrels (Falco sparverius) paired with males in captivity. Hormone levels and body weights for laying females were maximal during courtship and egg-laying periods, while those for non-layers showed no such distinct peaks. This demonstrated that these profiles were not controlled solely by photoperiod. Plasma corticosterone levels were elevated in all females during August and September when kestrels are preparing for migration. For laying females, body weight was positively correlated with plasma estrogen levels. A low spring body weight gain, and not stress, may have prevented the females from breeding in captivity. The photoperiodic control of molt did not appear to be mediated directly by the hormones studied, since there were no changes in hormone levels associated with the onset of molt.

Animals↗
PubMed1982

Gluten-sensitive enteropathy: sequence of villous regrowth as viewed by scanning electron microscopy.

Small-intestinal biopsy specimens from five children with gluten-sensitive enteropathy (GSE) were studied by scanning electron microscopy (SEM) before dietary treatment and sequentially after removal of gluten from the the diet. Compared with biopsy specimens from patients without evidence of villous atrophy, these specimens showed marked architectural changes. In patients with total villous atrophy observed by light microscopy, absent villi and prominent crypts were observed by SEM. Patients with subtotal villous atrophy had the first stages of villous formation characterized by semicircular ridge formation. Biopsy specimens obtained from the five patients with GSE after dietary treatment demonstrated a sequence of changes characterizing villous repair. The earliest change consisted of semicircular elevations of cells around the crypts. Unequal cellular repletion around the crypts and migration of the cells led to the formation of parallel ridges. Increased cell proliferation resulted in thickening and twisting of the ridges to form convoluted ridges. Increased complexity of the ridges appears to lead to the formation of cerebriform ridges, and septation at various points in the ridges results in the formation of mitten-like villi. In biopsy specimens from patients with villous atrophy from other causes, similar reparative changes were seen by SEM. Scanning electron microscopy is a useful adjunct to the light microscopic and dissecting microscopic assessment of small intestine biopsy specimens, and may be more sensitive tan light microscopy in documenting early morphologic response to dietary treatment for gluten-sensitive enteropathy.

Adolescent↗
PubMedDate not supplied

Functional integration of the transport of ammonium, glutamate and glutamine in astrocytes.

This short review surveys the effects of extracellular potassium, released by neuronal activity, on the fluxes of ammonium, glutamate and glutamine in astrocytes. There is evidence that each of these fluxes is modulated by potassium-induced changes in astrocytic pH. The result is viewed as an integrated response to neuronal activity. The unusually high permeability of astrocyte cell membrane to ammonium ions, together with the normal transmembrane gradient of pH, enables astrocytes to accumulate ammonium appreciably. However, at loci of neuronal activity, effective ammonium ion permeability is diminished and the cytosol is alkalinized, resulting in a local decline in intracellular ammonium concentration. Intracellular potassium concentration rises at these same loci, creating the conditions for a 'potassium-ammonium countercurrent' in which ammonium ions migrate intracellularly towards sites of neuronal activity as potassium ions diffuse away. Physiologic elevations of extracellular potassium evoke a marked 'paradoxical' increase in the velocity of glutamate uptake in astrocytes. This increase correlates well with the extent of potassium-induced alkalinization. Further, recent evidence identifies a major transporter of glutamine in astrocytes (System N) as a glutamine/proton exchanger. Potassium can reverse the transmembrane gradient of protons in astrocytes, and increase intracellular glutamine concentration, creating the conditions for a reversal of glutamine flux via System N from uptake to export. These flux changes, evoked by potassium released from active neurons, combine to accelerate glutamate-glutamine cycling.

Animals↗
PubMed2002

Somatostatin is a selective chemoattractant for primitive (CD34(+)) hematopoietic progenitor cells.

OBJECTIVE: Somatostatin (SST) is a regulatory peptide with a wide variety of activities in different tissues. SST activates G(alpha i)-protein-coupled receptors of a family comprising five members (SSTR1-5). Despite the broad use of SST and its analogs in clinical practice, the spectrum of activities of SST is incompletely defined. Here, we examined the role of SST and its receptors in hematopoiesis. MATERIALS AND METHODS: SSTR expression on human and mouse hematopoietic cells was analyzed by flow cytometry and reverse transcriptase polymerase chain reaction. The effects of SST on cell migration were measured in transwell assays. Using selective inhibitors, signaling mechanisms involved in SSTR2-mediated migration were studied in 32D cell transfectants expressing SSTR2. RESULTS: Human hematopoietic cells exclusively expressed SSTR2, whereas mouse bone marrow cells expressed SSTR2 and SSTR4. SSTR levels were high on primitive (CD34(+), Lin(-)) but low or absent on more mature (CD34(-), Lin(+)) cell types. Both SST and its analog octreotide acted as chemoattractants for primitive hematopoietic cells. Despite the presence of SSTR4, bone marrow cells from SSTR2-deficient mice failed to migrate toward SST gradients, suggesting that SSTR2 and SSTR4 are functionally different in this respect. SST activated phosphatidylinositol 3-kinase and the MAP kinases Erk1/2 and p38 in 32D[SSTR2] cells. While chemical inhibitors of these kinases had some effect, SST-induced migration was most strongly affected by blocking G(alpha i) activity or by elevating intracellular cAMP levels. CONCLUSIONS: Somatostatin acts as a selective chemoattractant for immature hematopoietic cells via activation of multiple intracellular pathways.

Animals↗
PubMed1998

Change in conformation of plasma membrane phospholipid scramblase induced by occupancy of its Ca2+ binding site.

Phospholipid (PL) scramblase is a 35.1 kDa plasma membrane protein that mediates the accelerated transbilayer migration of plasma membrane PL in activated, injured, or apoptotic cells exposed to elevated intracellular Ca2+. We recently identified a conserved segment in the PL scramblase polypeptide (residues Asp273 to Asp284) that is essential for its PL-mobilizing function and was presumed to contain the Ca2+ binding site of the protein (Zhou, Q., Sims, P. J., and Wiedmer, T. (1998) Biochemistry 37, 2356-2360). Whereas the sequence of this peptide segment resembles that of known Ca2+-binding loops within EF-hand containing proteins, it is unusual in being a single such loop in the entire protein and in being closely spaced to the predicted transmembrane helix (Ala291-Gly309). To gain insight into how Ca2+ activates the PL-mobilizing function of PL scramblase, we analyzed conformational changes associated with occupancy of this putative Ca2+ binding site. In addition to activation by Ca2+, the PL-mobilizing function of PL scramblase was found to be activated by other ions, with apparent affinities Tb3+, La3+ >> Ca2+ > Mn2+ > Zn2+ > Sr2+ >> Ba2+, Mg2+. Evidence for coordinate binding of metal ion by the polypeptide was provided by resonance energy transfer from protein Trp to Tb3+, which was competed by excess Ca2+. Metal binding to PL scramblase was accompanied by increased right-angle light scattering and by a prominent change in circular dichroism, suggesting that coordinate binding of the metal ion induces a conformational change that includes self-aggregation of the polypeptide. Consistent with this interpretation, addition of Ca2+ was found to protect PL scramblase from proteolysis by trypsin both in detergent solution as well as in situ, within the erythrocyte membrane. Mutation in the segment Asp273-Asp284 reduced Tb3+ incorporation and attenuated the change in CD spectrum induced by bound metal ligand, confirming that this suspected EF-hand loopike segment of the polypeptide directly contributes to the Ca2+ binding site.

Binding Sites↗
PubMed2000

Helicobacter pylori water-soluble surface proteins activate human neutrophils and up-regulate expression of CXC chemokines.

To elucidate the mechanisms of the persistent neutrophil recruitment in H. pylori-infected gastric mucosa, we evaluated the activation of human neutrophils and CXC chemokine expression in neutrophils by H. pylori water-soluble surface proteins. H. pylori water extract (HPWE) was prepared from a supernatant of the H. pylori suspension in distilled water. After neutrophils were stimulated with HPWE, the mobilization of intracellular free calcium, the expression of lymphocyte function-associated antigen-1beta, and the secretion of myeloperoxidase (MPO) were enhanced in the neutrophils. In H. pylori-infected gastric mucosa, transendothelial and transepithelial migration of neutrophils were observed by electron microscopy and mucosal MPO levels were elevated. Up-regulation of the expression of interleukin-8 (IL-8) and growth-related oncogenes (GROs; GROalpha, GRObeta and GROgamma) mRNA and protein in neutrophils by HPWE was demonstrated by quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. In conclusion, H. pylori-induced neutrophil recruitment may be mediated by CXC chemokines which are expressed by neutrophils activated by H. pylori water-soluble surface proteins.

Chemokines, CXC↗
PubMed1990

Characterization of a major development-regulated serum thyroxine-binding globulin in the euthyroid mouse.

We confirm our finding of a major development-regulated thyroxine-binding globulin (TBG) in the serum of the euthyroid mouse and investigate a number of its binding, structural and regulatory properties. Between 16 days foetal and 60 days postnatal life, the thyroxine (T4)- and tri-iodothyronine (T3)-binding activities of the sera show a striking ontogenic pattern: the binding is 2-3 times higher in foetuses than in mothers, then further increases after birth, reaching between 3 and 5 days maximum values which are 7-8 times higher than the adult ones. This pattern is not correlated with the ontogenesis of the acknowledged specific (transthyretin, TTR) and non-specific (albumin, alpha 1-foetoprotein) thyroid-hormone carriers of the mouse sera. PAGE studies demonstrate that the protein responsible for the elevated binding of the perinatal period is an alpha 1-globulin, with a migration similar to that of human and rat TBGs. Scatchard analysis is consistent with the notions that the T4-binding sites of TBG have high association constants, about two orders of magnitude above the T4 sites of TTR (10(9) M-1 as against 10(7) M-1) and low capacities (37 and 4 nmol/g of serum proteins in pups and adults respectively). Isoelectric focusing (i.e.f.) demonstrates that mouse TBG is a microheterogeneous protein separable, as a function of the pH gradient, in up to 10-12 isoforms, Marked shifts of the relative abundance of isoforms in the course of development are evidenced. The modulation of the TBG binding activity by non-esterified fatty acids (NEFA) and the control of its synthesis by the thyroid status are also reported. Mono- and poly-unsaturated NEFAs are strong inhibitors of the TBG, although they affect TTR less readily. On the other hand, the biosynthesis and/or secretion of TBG, but not of TTR, is under thyroid-hormone control, experimental hypothyroidism inducing a marked increase of the serum TBG. The TBG of mouse behaves as a highly significant parameter of development, pointing to a likely important function of the protein in the process of maturation. Our finding of major TBGs in both euthyroid rats and mice suggests that TBG is more widely spread than was thought until now, but difficult to detect in certain species outside definite maturation stages.

Aging↗
PubMed1996

Soluble CD4: a link between specific immune mechanisms and non-specific inflammatory responses?

The CD4 molecule is an important cell surface molecule expressed on many cell types including T-helper cells. CD4 can be shed from cells, and the truncated soluble form of CD4 (sCD4) has been found elevated in serum in several diseases. In this study the authors show that migration of polymorphonuclear neutrophils (PMN) is induced by sCD4. Histopathology of the site of injection of recombinant sCD4 in the skin shows local infiltration of PMN. In vitro, in Boyden chamber, sCD4 can rapidly give rise to a dose-dependent migration of PMN. The authors speculate that sCD4 can be another chemotactic factor and, as such, constitutes a link within the immune system between specific and non-specific elements of inflammation.

Animals↗