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PubMed2001

Therapeutic approach to chronic venous insufficiency and its complications: place of Daflon 500 mg.

Early manifestations of chronic venous insufficiency (CVI) are edema, hyperpigmentation, and lipodermatosclerosis. Late complications are cutaneous ulceration and delayed healing. The specific hallmarks of this inflammation include CD68-positive infiltration into the dermal tissue, monocytes, and lymphocytes and enhanced endothelial permeability. This may lead to "fibrin cuff" formation. In addition, membrane adhesion molecules are present and cytokine expression is seen. In one experimental model of mesenteric venous hypertension, the inflammatory process was detected in its earliest stages. This was evident in the form of neutrophilic leukocyte adhesion to venular endothelium as well as migration of cells across the endothelium and basement membrane into the interstitial space. Simultaneously, parenchymal cell death was detected. This suggests that the mechanism that triggers the inflammatory reaction is venous hypertension. This may cause venous distension and a shift in fluid shear stress. Our observations suggest that patients with venous insufficiency demonstrate circulatory humoral stimulators for leukocyte activation. Otherwise, there is evidence that the inflammatory reaction is limited to the region of the venous ulceration or at least to the skin areas with severe microangiopathy. It may be that activated leukocytes traverse perivascular cuffs and release active transforming growth factor-beta1 (TGF-beta1) which has been found to be elevated exclusively in areas of clinically active CVI. Surgical intervention markedly decreases the number of dysfunctional vein segments and allows pharmacologic agents to protect normal structures from continuing damage. Daflon 500 mg, the purified micronized flavonoid fraction containing 90% diosmin and 10% hesperidin, acts favorably in venous ulcer treatment by inhibiting the synthesis of prostaglandins and free radicals. It decreases bradykinin-induced microvascular leakage and may act favorably to inhibit leukocyte activation, trapping, and migration. Clinically, edema is reduced, ulcer healing is accelerated, and leukocyte trapping diminished. The action of micronized purified flavonoid fraction is beginning to be better understood, and as further knowledge is gained, better pharmacologic control of CVI is a tantalizing promise.

Animals↗
PubMed2000

Expression of intercellular adhesion molecule-1 (ICAM-1) in nasal epithelial cells of atopic subjects: a mechanism for increased rhinovirus infection?

Since clinical experimental studies indicate that upper respiratory tract viral infections may exacerbate acute asthma symptoms in atopic/asthmatic individuals, we have investigated the expression and modulation of ICAM-1 on human nasal epithelial cells (HNEC) from normal and atopic subjects. ICAM-1 is the attachment molecule for the majority of serotypes of human rhinovirus (HRV), including HRV-14, and is also critical for the migration and activation of immune effector cells. Basal ICAM-1 expression was significantly higher in HNEC obtained by brushings from atopic compared with non-atopic subjects (P = 0.031), and was also significantly increased on atopic HNEC harvested in season compared with out of season (P < 0.05). Atopic HNEC showed further up-regulation in ICAM-1 expression when cultured with clinically relevant allergen (P = 0.032). ICAM-1 levels on normal HNEC were also increased by infection with HRV-14 (P < 0.05). Basal expression of ICAM-1 on atopic nasal polyp epithelial cells (EC) was significantly higher than on both normal and atopic nasal HNEC. This elevated nasal polyp ICAM-1 level was not increased further by allergen, although HRV infection resulted in a small significant increase. Recovered viral titres from HRV-infected nasal polyp EC were 1.5-fold higher than from infected normal nasal HNEC. The data are consistent with the hypothesis that allergen, by enhancing expression of the HRV attachment target on host cells, facilitates viral infection in atopic subjects; simultaneously HRV-induced increases in ICAM-1 levels would favour migration and activation of immune effector cells to the airway, resulting in enhanced atopic inflammation.

Adult↗
PubMed2002

Lysophosphatidic acid induces focal adhesion assembly through Rho/Rho-associated kinase pathway in human ovarian cancer cells.

OBJECTIVE: The level of lysophosphatidic acid (LPA) is elevated in patients with ovarian cancer, and LPA has been reported to have a pivotal role in cancer dissemination. In the current study, the effect of LPA on the motility of ovarian cancer cells was investigated. METHODS: We analyzed the effects of LPA on the migration activity, the focal adhesion formation, and the tyrosine phosphorylation of focal adhesion proteins in human ovarian cancer cell lines Caov-3 and OVCAR-3. Inhibitors of the small GTPase Rho, one of its downstream effectors (Rho-associated kinase (ROCK)), myosin light chain kinase (MLCK), and myosin light chain (MLC) phosphatase were used to examine the mechanism of LPA-induced cellular effects. RESULTS: LPA enhanced the migration of ovarian cancer cells and facilitated their invasion. Rho and ROCK played essential roles in the migratory process, as evidenced by the inhibition of migration and focal adhesion formation of cancer cells by Clostridium botulinum C3 exoenzyme (C3), an inhibitor of Rho, or Y-27632, an inhibitor of ROCK. LPA also evoked the formation of focal adhesions and tyrosine phosphorylation of focal adhesion kinase and paxillin, all of which were inhibited by C3 or Y-27632. CONCLUSION: These results suggest that LPA induced the migration of ovarian cancer cells, at least in part, through accelerated formation of focal adhesions mediated by Rho/ROCK-induced actomyosin contractility. This study may provide the basis for new therapies to control the metastasis of ovarian cancer.

Cell Movement↗
PubMed1985

Monolayer culture of pancreatic islets from the Syrian hamster.

Pancreatic islets of Langerhans of the Syrian hamster were maintained in culture for as long as 43 wk. Islets were prepared by collagenase/hyaluronidase digestion of minced pancreas. The islets quickly attached to the plastic culture flasks and lost their spherical form as they flattened out to form circular monolayers. Few fibroblastoid cells were observed. As outward migration continued, the islets became vacuolated with the ultimate formation of monolayer rings. Throughout the culture period the beta cells continued to synthesize and secrete insulin. Furthermore, the cells maintained a responsiveness to glucose stimulation with increased rates of hormone secretion in the presence of elevated concentrations of the sugar. These studies demonstrate the suitability of Syrian hamster islets for studies involving long-term culture.

Animals↗
PubMedDate not supplied

Transcatheter embolization of a renal artery aneurysm using ethylene vinyl alcohol copolymer.

Our aim was to treat a clinically silent renal artery aneurysm. The patient was a 76-year-old man with elevated prostate-specific antigen and prostate biopsies with a grade II-III adenocarcinoma who was incidentally found to have an aneurysm in his right renal artery. We performed a successful transcatheter embolization of the aneurysm using ethylene vinyl alcohol copolymer (Onyx). To avoid migration of the liquid material into the parent artery, a balloon was inflated in the orifice of the neck of the aneurysm while the liquid was injected. Five-month follow-up computed tomography (CT) imaging confirmed total occlusion of the aneurysm.

Aged↗
PubMed1996

Moving boundary electrophoretically mediated microanalysis.

Moving boundary sample introduction is described as an alternative to zonal injection methods for the electrophoretically mediated microanalysis (EMMA) of leucine aminopeptidase (LAP). The capillary was initially filled with the analyte solution while the faster-migrating substrate, L-leucine-p-nitroanilide, was maintained in the inlet reservoir. Upon application of an electric field, electrophoretic merging of the reagents proceeded, and the detectable reaction product, p-nitroaniline, was transported to the detector. The area, maximum height, inclining slope, and declining slope of the resulting triangular product profile were each directly proportional to the activity of LAP, and the observed migration times of the product profile features defined the volume and time of the incubation. The moving boundary technique offered more than an order of magnitude greater concentration sensitivity than the zonal injection EMMA method. This heightened sensitivity facilitated rapid analysis as the use of elevated electric field strenghts and short capillaries allowed for a 24-s kinetic determination of LAP.

Animals↗
PubMed1997

Ca2+-triggered peptide secretion in single cells imaged with green fluorescent protein and evanescent-wave microscopy.

Green fluorescent protein fused to human chromogranin B or neuropeptide Y was expressed in PC12 cells and caused bright, punctate fluorescence. The fluorescent points colocalized with the endogenous secretory granule marker dopamine beta-hydroxylase. Stimulation of live PC12 cells with elevated [K+], or of permeabilized PC12 cells with Ca2+, led to Ca2+-dependent loss of fluorescence from neurites. Ca2+ stimulated secretion of both fusion proteins equally well. In living cells, single fluorescent granules were imaged by evanescent-wave fluorescence microscopy. Granules were seen to migrate; to stop, as if trapped by plasmalemmal docking sites; and then to disappear abruptly, as if through exocytosis. Evidently, GFP fused to secreted peptides is a fluorescent marker for dense-core secretory granules and may be used for time-resolved microscopy of single granules.

Animals↗
PubMed2006

Reciprocal regulation of RhoA and RhoC characterizes the EMT and identifies RhoC as a prognostic marker of colon carcinoma.

Understanding how RhoC expression and activation are regulated is essential for deciphering its contribution to tumorigenesis. Here, we report that RhoC expression and activation are induced by the epithelial to mesenchymal transition (EMT) of colon carcinoma. Using LIM 1863 colon cancer cells, RhoC protein expression and subsequent activation were detected coincident with the loss of E-cadherin and acquisition of mesenchymal characteristics. Several Ets-1 binding sites were identified in the RhoC promoter, and evidence was obtained using chromatin immunoprecipitation that Ets-1 can regulate RhoC expression during the EMT. Interestingly, a marked decrease in RhoA activation associated with the EMT was observed that corresponds to the increase in RhoC expression. Use of shRNA established that RhoA inhibits and RhoC promotes post-EMT cell migration, demonstrating functional significance for their coordinate regulation. To assess the importance of RhoC expression in colon cancer, immunohistochemistry was performed on 566 colorectal tumors with known clinical outcome. The level of RhoC ranged from no expression to high expression, and statistical analysis revealed that elevated RhoC expression correlates with poor outcome as well as aberrant expression and localization of E-cadherin. These data provide one mechanism for how RhoC expression is regulated in colon carcinoma and substantiate its utility as a prognostic marker.

Biomarkers, Tumor↗
PubMedDate not supplied

Studies on coronary arteriopathy in dogs following administration of CI-1020, an endothelin A receptor antagonist.

A selective nonpeptide endothelin A (ETA) receptor antagonist, CI-1020, was administered to beagle dogs intravenously (i.v.) for 4 hours to 4 weeks. One animal/sex received CI-1020 at 1 mg/kg/hr intravenously for 4, 8, or 24 hours to investigate onset of arteriopathy. Control animals (1/sex) received the vehicle only. To determine reversibility of arteriopathy, 8 dogs/sex were given CI-1020 at 1 mg/kg/hr for 4 days. Two dogs/sex were sacrificed 1, 3, 8, and 29 days following cessation of infusion. Lesion development with prolonged exposure was investigated in 1 male dog. It was given CI-1020 by i.v. bolus at 120 mg/kg/day for 4 weeks and Monastral blue dye was administered i.v. to facilitate localization of vascular lesions. Coronary blood flow was determined in 4 dogs infused with CI-1020 at 0.3, 3, and 30 mg/kg for one hour at each dose. Macroscopically, hemorrhage or blue discoloration of Monastral blue was noted in the extramural coronary arteries along the coronary groove and atrium. Histologically, the earliest coronary changes were noted in animals sacrificed after 24 hours of treatment and characterized by medial hemorrhage and necrosis with a few infiltrating neutrophils. In the reversibility study, incidence and severity of arteriopathy was dependent on time of sacrifice following cessation of infusion. Acute necrotizing inflammation of arteries was present in all animals (n = 4) on day 1 postinfusion, whereas on day 8 postinfusion, lesions characterized by medial small pockets of trapped red cells, cell debris, and adventitial thickening were seen in 1 dog/sex. By day 29 postinfusion, coronary arteries were similar to controls. In the dog given daily i.v. bolus injections of CI-1020 for 4 weeks, arterial inflammatory lesions varied from acute to chronic, although most lesions were considered chronic active. Monastral blue pigments were noted in the wall of most arteries with chronic or chronic active lesions. Acute lesions were similar to those noted in day 1 postinfusion of the reversibility study. Medial smooth muscle necrosis and/or fibrosis with mixed inflammatory cell infiltrates characterized chronic or chronic active lesions. Smooth muscle proliferation and migration into the intima were also noted. There were no significant changes in coronary blood flow, coronary vascular resistance, or mean arterial blood pressure following CI-1020 infusion for 3 hours. In the 24-hour infusion study, plasma endothelin 1 (ET-1) levels were mildly elevated (1.5-4 fold) during CI-1020 infusion when compared to either pretest or control values. These results indicate that administration of endothelin antagonist (CI-1020) to dogs was associated with development of coronary arteriopathy, which was completely resolved within 29 days following cessation of treatment. With prolonged (4-week) CI-1020 treatment, arterial lesions at varying stages of development (acute, chronic active, chronic) were seen, suggesting that tolerance to treatment (up to 4 weeks) does not occur.

Actins↗
PubMed2006

Mice overexpressing p40 in lungs have reduced leucocyte influx and slightly impaired resistance during tuberculosis.

Interleukin (IL)-12 (p70) is a heterodimeric cytokine composed of p40 and p35, that plays a major role in the protective immune response to Mycobacterium tuberculosis. To define the role of p40 in lungs during pulmonary M. tuberculosis infection we generated transgenic (Tg) mice overexpressing p40 under control of the surfactant protein C promoter. Tg mice expressed the transgene in their lungs, yet demonstrated elevated pulmonary p40 protein levels. After infection, Tg mice displayed higher pulmonary p40 and p70 levels than wild type mice. Interferon-gamma concentrations were similar in uninfected and infected Tg and wild type mice, arguing against agonistic effects of p40. Tg mice demonstrated reduced recruitment of macrophages, lymphocytes and neutrophils to the lungs early after infection. This was accompanied by reduced pulmonary tumour necrosis factor-alpha, macrophage inflammatory protein (MIP)-2 and MIP-1alpha levels. This suggests that elevated p40 concentrations inhibited the chemotactic effects of p70 on leucocytes. Furthermore, Tg mice displayed slightly higher pulmonary mycobacterial outgrowth late in the infection than wild type mice. Taken together, we demonstrate that constitutive overexpression of p40 in lungs negatively influences IL-12-mediated leucocyte migration and protection against lung tuberculosis. This suggests a novel antagonistic role for p40 homodimers in regulating the chemotactic bioactivity of IL-12 after pulmonary mycobacterial infection.

Animals↗
PubMed1995

Expression of platelet-derived growth factor ligands and receptors by rat aortic endothelium in vivo.

In situ hybridization and immunostaining were used to study the time course of expression for platelet-derived growth factor (PDGF) ligands and receptors in endothelium of the rat aorta after injury. The PDGF-A and -B chains were expressed in endothelial cells at the wound edge within 4 h after injury, but no expression was detectable in uninjured endothelium. PDGF alpha-receptor was expressed in a pattern similar to the PDGF-A chain, while expression of PDGF beta-receptor was not detected at any time. Expression of the PDGF-B chain remained elevated in endothelial cells at the leading edge even at later measurements when these cells had stopped replicating. Smooth muscle cells (SMCs), which are absent from the intima of the normal aorta and are known to express PDGF beta-receptors, were predominantly found to migrate into the intima near the endothelial leading edge where PDGF-B was expressed. These data suggest a paracrine role for endothelial PDGF in SMC migration.

Animals↗
PubMed2006

Activation of p70S6K induces expression of matrix metalloproteinase 9 associated with hepatocyte growth factor-mediated invasion in human ovarian cancer cells.

The expression of hepatocyte growth factor (HGF) receptor, encoded by the Met oncogene, is elevated in ovarian and a variety of cancers. Here we show that human ovarian cancer cells with high Met expression were more sensitive to the cell motility and invasion effect of HGF. Met down-regulation by small interfering RNAs or K252a resulted in reduced migration in response to HGF. The invasive/migratory phenotype activated by HGF can be blocked by specific inhibitors of the phosphatidylinositol-3-kinase (PI3K) cascade, inhibitor of p70(S6K), and also the expression of a dominant-negative Akt, demonstrating that HGF transmits the motogenic signal through PI3K and Akt to p70(S6K). A significant role for p70(S6K) in cell invasion is further supported by the observation that expression of constitutively active forms of p70(S6K) is sufficient to induce invasive and migratory phenotypes in ovarian cancer cells. Importantly, activation of p70(S6K) stimulated expression and proteolytic activity of matrix metalloproteinase (MMP)-9 and cellular invasion, whereas it had little effect on MMP-2, suggesting for the first time that MMP-9 up-regulation by p70(S6K) as a key step for HGF-induced invasion and migration. These data suggest that interfering p70(S6K) may provide a novel means of controlling tumor cell invasiveness.

Acetylcysteine↗
PubMed2005

Neurogenesis and neuroprotection induced by peripheral immunomodulatory treatment of experimental autoimmune encephalomyelitis.

Brain insults such as the autoimmune inflammatory process in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) induce a measure of neurogenesis, but its regenerative therapeutic consequence is limited, because it fails to regenerate functional neurons and compensate the damage. Here, we investigated whether peripheral immunomodulatory treatment for MS/EAE, glatiramer acetate (GA), can enhance neurogenesis and generate neuroprotection in the CNS of EAE-inflicted mice. EAE was induced by myelin oligodendrocyte glycoprotein peptide, either in yellow fluorescent protein (YFP) 2.2 transgenic mice, which selectively express YFP on their neuronal population, or in C57BL/6 mice. The in situ effect of GA was studied in various brain regions; neuroprotection and neurogeneration were evaluated and quantified by measuring the expression of different neuronal antigens and in vivo proliferation markers. The results demonstrated that in EAE-inflicted mice, neuroproliferation was initially elevated after disease appearance but subsequently declined below that of naive mice. In contrast, GA treatment in various stages of the disease led to sustained reduction in the neuronal/axonal damage typical to the neurodegenerative disease course. Moreover, three processes characteristic of neurogenesis, namely cell proliferation, migration, and differentiation, were augmented and extended by GA treatment in EAE mice compared with EAE-untreated mice and naive controls. The newborn neuroprogenitors manifested massive migration through exciting and dormant migration pathways, into injury sites in brain regions, which do not normally undergo neurogenesis, and differentiated to mature neuronal phenotype. This suggests a direct linkage between immunomodulation, neurogenesis, and an in situ therapeutic consequence in the CNS.

Animals↗
PubMed2006

[Suicide among migrant populations and native Dutch in The Netherlands].

OBJECTIVE: To determine the differences in suicide mortality between native Dutch and migrant groups in the Netherlands from different countries and regions of origin, taking the differences in age structure into account. DESIGN: Retrospective. METHODS: Data from the statistics on causes of death from the Dutch Central Bureau of Statistics, Statistics Netherlands (CBS), based on the causes of death given in the certificates from the doctor or forensic pathologist, were coupled to the reports of death from the Municipal Population Registration (GBA). In this way, the country of origin of the deceased could be determined. The confidentiality of these data is regulated by law. For the period 1996-2004, all 13,737 persons were selected who had committed suicide (International classification of diseases (ICD)-10-codes X60-X84). The country of origin was determined on the basis of data on the country of birth of the deceased and his or her parents. Someone is a 'migrant' ('foreign') according to the definition of the CBS if at least one of the parents was born outside the Netherlands. RESULTS: There were substantial differences in suicide mortality between migrant groups in the Netherlands. These differences reflected, to some extent, suicide mortality patterns in the countries and regions of origin. On the whole, migrants originating from western countries showed suicide mortality rates that were well above the average rate for native Dutch. High suicide rates were seen in male migrants from southern and eastern Europe. On the other hand, suicide mortality was significantly lower among Turks and Moroccans than among native Dutch. Only young adult males of non-western origin, with the exception of Moroccans, were much more likely to commit suicide than native Dutch. CONCLUSION: Although much attention has recently been paid to the elevated rates of attempted suicide among young women from Surinam, their suicide mortality was increased less than that of men from Surinam up to middle age. These increased suicide rates may reflect high levels of mental illness, identity problems, disappointments related to the process of migration, high expectations with respect to education, work and income, and the responsibilities for a family.

Adolescent↗
PubMedDate not supplied

A study of cell-mediated immunity and histocompatibility antigens in leprosy patients in Iran.

Fifty-six male and 14 female leprosy patients, aged 11-62, were studied for cell-mediated immunity (CMI) and histocompatibility antigens. Healthy blood donors were used as normal controls. All patients were receiving antileprosy drugs. T and B cells were detected by E and EAC rosette formation technics, and the leukocyte migration test (LMT) was done in the presence of PHA. HLA antigens were defined by a modified N.I.H. lymphocytotoxicity test in order to type 48 patients and 100 controls. There was a significant difference (p less than 0.01) in the number of T cells between tuberculoid and lepromatous forms of the disease as compared to normal controls. We did not observe any differences in EAC rosette cells. It should be noted that the migration index is significantly higher in controls than in leprosy patients for PHA. There are no significant differences in the distribution of the A locus antigens between leprosy patients and controls, although a higher percentage of A-11 was obtained in leprosy patients. A slight elevation of B5 antigen was observed but these results are preliminary and our information regarding the B locus is incomplete. Thus, it is difficult to establish any precise relationship between HLA antigen and leprosy at this stage.

Adolescent↗
PubMed1976

[Kinetics of the colony-forming capacity of bone marrow cells following hydrocortisone administration to mice].

A study was made of the dynamics of the colony-forming and migration capacity of the polypotent stem hemopoietic cells of the bone marrow of the F1 (CBA X C57BL) mice after the hydrocortisone administration. The relative count of the stem hemopoietic cells in the bone marrow increased on the 3rd day after the hydrocortisone administration. This elevation was maximal on the 5th day after the hydrocortisone administration. On the 8th day the stem hemopoietic cell count decreased to the normal level.

Animals↗
PubMed2006

Effect of waterborne exposure to 4-tert-octylphenol and 17beta-estradiol on smoltification and downstream migration in Atlantic salmon, Salmo salar.

Groups of Atlantic salmon parr (November, Exp. 1) or pre-smolts (March, Exp. 2) were exposed to estradiol-17beta (E2 conc.: nominal 500 ngl(-1)/actual 8-16 ngl(-1)) and two doses of tert-octylphenol (OP: nominal 25 microgl(-1)/actual 4.5-6.5 microgl(-1) and OP: nominal 100 microgl(-1)/actual 10-30 microgl(-1)) for 26 days in fresh water, and the effects on physiological and behavioural aspects of parr-smolt transformation were investigated. Vitellogenesis was induced by all treatments, as indicated by elevated levels of plasma vitellogenin (Vtg) and hepatosomatic index. Elevated Vtg levels were still found in OP-100 and E2-treated fish 4-5 months after cessation of treatment, indicating a slow clearance of Vtg from circulation. Smolting was compromised by E2 and OP-100 treatment as judged by reduced gill Na(+), K(+)-ATPase activity and impaired ability to regulate plasma osmolality and muscle water content in 24-h sea water (SW) challenge tests during the period of smolting. Downstream migratory behaviour was monitored from late April to July (Exp. 2) by implanting passive integrated transponder tags into subgroups of treated and control smolts and placing them in a stream raceway. Irrespective of treatment, nocturnal downstream movement was initiated in all groups on April 23, switching to diurnal movement in late May. Average swimming speed was estimated to be higher than current speed, indicating active migration. E2 and OP-100 fish migrated at lower frequency than control fish, suggesting a reduced migratory drive. The data suggests that waterborne exposure of salmon to xenoestrogens reduce both physiological and behavioural components of smoltification, even when exposure occurs several months prior to smolting.

Animal Migration↗
PubMed2005

Antiprotease inactivation by Salmonella enterica released from infected macrophages.

The mammalian serine protease plasmin, which has an important role in extracellular matrix degradation during cell migration, is regulated by the plasma antiprotease alpha(2)-antiplasmin (alpha(2)AP). The surface protease PgtE of Salmonella enterica serovar Typhimurium proteolytically inactivated alpha(2)AP. PgtE also activates the plasma zymogen plasminogen to plasmin, and bacteria expressing PgtE promoted degradation of extracellular matrix laminin in the presence of plasminogen and alpha(2)AP. alpha(2)AP inactivation was detected with the rough derivative of S. enterica 14028, but not with the smooth wild-type strain, suggesting that the O-antigen of lipopolysaccharide prevented contact of PgtE with the substrate molecule. After growth of S. enterica 14028 in murine J774A.1 macrophage-like cells, the infected cell lysate as well as bacteria from isolated Salmonella-containing vacuoles (SCVs) cleaved alpha(2)AP. Bacteria from SCVs produced an elevated level of PgtE and had a reduced O-antigen chain length. The lysate from S. enterica 14028-infected macrophages promoted formation of plasmin in the presence of alpha(2)AP, whereas plasmin formation by lysates from uninfected macrophages, or from macrophages infected with the pgtE-negative derivative of 14028, was inhibited by alpha(2)AP. Salmonella disseminates in the host within macrophages, which utilize plasmin for migration through tissue barriers. The results suggest that intracellular enhancement of PgtE activity in Salmonella may promote macrophage-associated proteolysis and cellular migration by altering the balance between host plasmin and alpha(2)AP.

Animals↗