Biomedical subjects

M Reale

Publications and source records attributed to M Reale.

At least 37 records · Page 2Linked to original sources

PubMed1999

Vitamin B6-deficient diet plus 4-deoxypyridoxine (4-DPD) reduces the inflammatory response induced by T. spiralis in diaphragm, masseter and heart muscle tissue of mice.

Animals fed diets deficient in vitamin B6 develop microcytic anemia, alterations of growth, and other pathologies. 4-deoxypirydoxine is a potent antagonist of vitamin B6 coenzyme which depresses IL-1, TNF and IL-6 and has anti-inflammatory properties. The aim of this study was to show the anti-inflammatory effects of 4-DPD on chronic inflammation caused by the nematode parasite T. spiralis, specifically on the recruitment and the activation of inflammatory cells. Two groups of mice, 6 weeks of age, were used: one was maintained on a vitamin B6-deficient synthetic pellet diet for 15 days before injection of the nematode, and administered an intraperitoneal injection (i.p.) of 4-DPD (250 microg/mouse) for 15 days (the first, 5 days before infection), and the second group was maintained on a normal diet for the total duration of the experiment. These two groups were then injected with 150 larvae (L1-T7 spiralis) per os. Chronic inflammation was caused by infection of treated or untreated mice with T7 spiralis parasite. After 14 days post-infection all mice developed a chronic inflammatory response. Mice fed with a B6-deficient diet showed a significant decrease in the number of cysts found in the diaphragm when compared to mice treated with normal diet. In addition, in all mice treated with vitamin B6-deficient diet plus 4-DPD the average body weight was significantly lower, compared to the mice on normal diet in all weeks examined. Moreover, in sections of the diaphragm, masseter and myocardium muscles, the infiltration of inflammatory cells, such as macrophages, lymphocytes, and eosinophils were more intense in untreated mice compared to those fed a vitamin B6-deficient diet. These results show that BALB/c mice infected with T. spiralis and fed a vitamin B6-deficient diet plus the vitamin B6 antagonist, 4-DPD, prolong the time of invasion of the larvae in the muscle cells, influence the recruitment of inflammatory cells and the intensity of the inflammatory reaction compared to infected untreated mice (control).

Animals↗

PubMed1999

IgG, IgG1 and IgM response in Trichinella spiralis-infected mice treated with 4-deoxypirydoxine or fed a Vitamin B6-deficient diet.

The aim of this study was to investigate the effect of pyridoxine (Vitamin B6) deficiency on the immunological response of BALB/c mice infected with the parasite T. spiralis. Specific anti-parasite IgM and IgG immunoglobulins were detected by ELISA method in the serum of treated animals at different periods for 60 days post infection. Vitamin B6-deficiency was induced in two separate groups of mice by either (1) maintaining the mice on a Vitamin B6-deficient synthetic pellet diet for 40 days before infection, or (2) by daily intraperitoneal injection of 8 x 10(5) M/100 microl of 4-Deoxypyridoxine (4-DPD), a potent antagonist of Vitamin B6 for 20 days prior to infection. These two groups of mice were then injected with 100 larvae (L1-T. spiralis) per os. Parasite burdens in the mice were observed by light microscopy. Cysts were present in the diaphragms of the mice after 60 days post-infection. Parasite specific IgG, as well as IgG1 levels were determined in the sera of infected mice fed a normal diet. These levels were found to be lower in the 4-DPD-treated mice compared to the untreated mice. The inhibition started from the 10th day and continued to the 60th day, and in the 4-DPD-treated group the inhibition initiated after 24 h to 60 days. IgM level also was depressed by 4-DPD, starting from 24 h after injection of the compound. In mice fed Vitamin B6-deficient diets the levels of IgG were lower than in mice fed normal diets. These results show that BALB/c mice infected with T. spiralis and fed either a Vitamin B6-deficient diet or a diet which included the Vitamin B6-antagonist, 4-DPD, both influence the course of IgG, IgG1 and IgM production.

Animals↗

PubMed1999

Impact of extremely low frequency electromagnetic fields on CD4 expression in peripheral blood mononuclear cells.

There is increasing evidence suggesting that extremely low frequency electromagnetic fields (ELF-EMF) may influence several cell functions. Here the effects of ELF-EMF were studied on the expression of CD4+ cell surface receptors of human peripheral blood mononuclear cells (PBMC) using fluorescence-activated cell sorter (FACScan). The expression of CD4+ in ELF-EMF exposed (24, 48 and 72 h) and not exposed PBMC were not statistically significant. In addition, a flow cytometric analysis was determined by using a fluorescent labeled antibody, at 24 and 72 h incubations. The amount of bound antibody was distributed with a slight difference in the ELF-EMF-exposed PBMC compared to the not exposed cells. Moreover, DNA CD4+ expression in PBMC strongly increased in exposed cells, resting and activated with Phytohaemaglutinin (PHA). When polymerase chain reaction was performed on CD4+ mRNA of PBMC an increase of CD4+ mRNA expression was found after the resting cells were exposed to ELF-EMF at 24 h compared to not exposed cells, while at 48 and 72 h no difference was found. In the cell cycle progression analysis, the PBMC exposed to ELF-EMF presented a significant increase of percentage expression of cell cycle progression in the S phase compared to not exposed cells; while in G1 and G2 phases, there were no differences. Our results provide new evidence that ELF-EMF can affect CD4+ expression in PBMC and describe an additional biological activity for ELF-EMF affecting CD4+ transcription and translation protein and the increase of the percentage expression of the cell cycle progression of the S phase.

Blotting, Western↗

PubMed1998

Transforming growth factor beta1 induces IL-1 receptor antagonist production and gene expression in rat vascular smooth muscle cells.

Atherosclerosis is an inflammatory-fibroproliferative process that may represent a possible milieu in which transforming growth factor-beta (TGF-beta) can be involved. Vascular smooth muscle cells (VSMC) may represent a source or a target of a large number of growth factors and proinflammatory cytokines, including interleukin-1 and its receptor antagonist (IL-1Ra). We tested the effect of TGF-beta1, on IL-1Ra production and gene expression in rat VSMC cultures. We found a significant dose (3-30 ng/ml) and time-dependent (0-48 h) increase in IL-1Ra immunoactivity in the supernatant of conditioned medium and cell lysates. The maximal effect was observed with TGF-beta at 30 ng/ml and after 24 h incubation time, respect to untreated cells (320 +/- 26 vs. 211 +/- 20 pg/ml; P < 0.01). Furthermore, TGF-beta1 induced an increased mRNA expression which began at 2 h and peaked at 18 h incubation time (about a 6-fold increase with respect to unstimulated cells). The effect of TGF-beta1 on IL-1Ra production was completely inhibited by an anti-IL-1beta antibody (10 microg/ml) (from 320 +/- 81 to 181 +/- 46 pg/ml). These experiments suggest that TGF-beta1, potentially produced in the vascular wall during atherogenesis, may play a pathophysiological role in the autocrine control of IL-1 actions, via VSMC IL-1Ra production.

Animals↗

PubMed1998

Induction of monocyte chemotactic protein-1 (MCP-1) and TNF alpha by Trichinella spiralis in serum of mice in vivo.

MCP-1 is a small (8-10 KDa) protein and a prototype member of the CC chemokine beta subfamily, which plays a critical role in acute and chronic inflammation. Recent evidence suggests an important role for MCP- 1, MCP-2 and MCP-3 in a number of pathological states, including delayed type hypersensitivity conditions, parasitic infections and rheumatoid arthritis. Forty BALB-c mice were treated with the parasite Trichinella spiralis. After the infection the animals were sacrificed at different periods from the initial infection and MCP-1 and TNFalpha were quantified in the mouse serum. The level of MCP-1 in the serum of mice infected with 100 larvae increases from 27.5+/-7.0 pg/ml at day 23, to a maximum level of 31.5+/-5.0 pg/ml at day 33, then decreased to 14.6+/-2.0 pg/ml at day 47. When the mice were infected with 200 larvae of T. spiralis the maximum increase was 34.4+/-2.5 pg/ml found on day 23. From day 33 to day 47 MCP-1 levels were decreased. In addition, in infected mice levels of TNFalpha were detectable in the serum as early as day 1. The level of TNFalpha was maximum at day 35 (3812+/-224 pg/ml). Serum from non-infected mice contained no detectable levels of either MCP-1 or TNFalpha. However, even if MCP-1 seems to be implicated in Trichinellosis, its exact role and function in inflammatory parasitic diseases remains to be determined.

Animals↗

PubMed1998

Mast cell recruitment after subcutaneous injection of RANTES in the sole of the rat paw.

The effect of hrRANTES was studied after the injection in the sole of the rat paw, an area particularly rich in mast cells. Subcutaneous injections of RANTES 50 ng/10 microl produced an erythematous reaction which was inhibited by anti-RANTES antibody 50 microg/rat injected in the tail vein 30 min before hrRANTES 50 ng/10 microl was injected. In another set of experiments the animals were injected subcutaneously in the sole of the paw with PBS 10 microl (control), LPS (100 ng/10 microl) hrRANTES 50 ng/10 microl or anti-RANTES 50 microl/rat injected in the tail vein 30 min before hrRANTES 50 ng/10 microl was injected. The biopsies were analysed after 4 h and counted in an optic field. hrRANTES produced a strong recruitment of mast cells selectively coloured with 0.1% toluidine blue and inhibited by anti-RANTES antibody. In addition to the optical and electron microscope study, in some of the excised tissue Northern blot analysis for histidine decarboxylase (HDC) mRNA was performed to estimate the amount of histamine generation in the tissue of the injection sites. We found that subcutaneous injections of hrRANTES 50 ng/10 microl in the sole of the rat paw produced an accumulation of a great number of mast cells compared to PBS 10 microl (negative control) or LPS 100 ng/10 microl (positive control) after 4 h. The hrRANTES effect was inhibited by anti-RANTES antibody injected in the tail vein 30 min before hrRANTES exposure. Moreover, hrRANTES increased HDC mRNA and histamine generation.

Animals↗

PubMed1998

Intramuscular injection of hrRANTES causes mast cell recruitment and increased transcription of histidine decarboxylase in mice: lack of effects in genetically mast cell-deficient W/WV mice.

RANTES (regulated upon activation, normal T cell expressed and presumably secreted) and other chemoattractant proteins are members of the intercrine or chemokine family of proinflammatory basic polypeptides. RANTES is a prototype of the C-C chemokine subfamily that acts as a selective chemoattractant for human monocytes and CD4-positive lymphocytes and increases the adherence of monocytes to endothelial cells. However, the role of RANTES in white cells is still unclear. We report here that hrRANTES at 20 ng/50 microl in mice causes mast cell recruitment 4 h after intramuscular injection, an effect inhibited by anti-RANTES, as evidenced by 0.1% Toluidine blue, a specific dye for coloring mast cells. Injections of PBS (50 microl) vehicle (negative control) did not produce any appreciable inflammatory response, whereas injection of lipopolysaccharide 20 ng/50 microl (positive control) generated a marked inflammatory state. When RANTES was injected intramuscularly in genetically mast cell-deficient W/Wv mice, the inflammatory effect was not present. The RANTES injection sites were then excised and studied under an optical and electron microscope. A Northern blot analysis was performed using a probe that was prepared to detect mRNA encoding the histidine decarboxylase (HDC) gene on excised muscle tissue. We found that hrRANTES provoked generation of HDC mRNA from muscle tissue after 4 h. These effects were inhibited by an anti-RANTES antibody and were absent in genetically mast cell-deficient mice. The increasing number of mast cells in the RANTES injection sites led to an augmentation of histamine content compared to controls (PBS). The injection of hrRANTES 20 ng/20 microl into the sole of a rat paw confirmed the inflammatory and the mast cell recruitment potential of this chemokine. In these studies, hrRANTES injections in muscle tissue provided direct in vivo evidence that RANTES has a significant effect on mast cell recruitment and HDC mRNA generation.

Animals↗

PubMed1998

Serum levels of soluble adhesion molecules in chronic renal failure and dialysis patients.

Besides cell-bound adhesion molecules, which are of fundamental importance to a large number of physiological and pathological processes, soluble forms of adhesion molecules have been detected in the circulating blood in recent years. Circulating soluble adhesion molecules appear to be biologically active, and raised levels have been reported in a variety of disorders. In the present study, we used ELISA to measure the serum levels of four soluble adhesion molecules in 23 undialyzed patients with chronic renal failure (CRF), 13 patients on continuous ambulatory peritoneal dialysis (CAPD), 17 on chronic hemodialysis (HD) and 18 healthy controls having a similar mean and distribution of ages. The investigated soluble (s) molecules included intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1), sE-selectin and sP-selectin. sICAM-1 was found to be elevated in patients with CRF (p < 0.05), on CAPD (p < 0.02) and HD (p < 0.0001) compared with the controls but levels did not differ between the three patient groups. The higher sVCAM-1 values found in CRF (p < 0.02), CAPD (p < 0.05) and HD (p < 0.0001) as compared to controls again failed to differentiate the three groups of patients. Soluble E-selectin was also raised in the three groups (p < 0.0001) with no difference between them. Increased sP-selectin was found in CRF (p < 0.05), CAPD (p < 0.02) and in HD patients (p < 0.0001) compared to controls, and levels in HD were significantly higher (p < 0.02) than in CRF patients. Predialysis serum molecule levels did not differ between HD patients treated with cuprophan or with polyacrylonitrile dialyzers. HD sessions with both dialyzers had no effect on sICAM-1, while a decrease (p < 0.02) in sP-selectin was found after dialysis with cuprophan. In undialyzed patients with CRF, regression analysis showed a strong linear correlation between serum creatinine and serum levels of each soluble molecule. These results demonstrate that serum levels of soluble adhesion molecules ICAM-1, VCAM-1, E-selectin and P-selectin are elevated in both undialyzed patients with CRF and patients on CAPD or HD. The elevated serum levels of these proteins probably reflect inadequate clearance as well as enhanced synthesis/release.

Adult↗

PubMed1998

[Transluminal percutaneous angioplasty of stenosis of arteriovenous fistulas; 24-month follow-up].

Stenosis is a common cause of the functional loss of vascular shunts used in chronic hemodialysis and percutaneous transluminal angioplasty represents the elective method to correct these anomalies. A total of 42 percutaneous transluminal angioplasties were performed, with a prospective study and follow-up lasting an average of 18 months, in 32 patients with insufficient blood flow of arteriovenous fistula. In over 90% of cases the procedure restored adequate hemodynamic conditions that remained unchanged during follow-up. The authors therefore conclude that percutaneous transluminal angioplasty is an efficacious, easily performed and low-cost method that does not present major complications.

Adult↗

PubMed1998

Portable fluoroscopic X-ray systems and traditional fixed angiographic systems: a comparison in the detection of coronary stenosis.

INTRODUCTION: The ability to perform coronary angiography at the bedside has multiple applications. METHODS: In this study, we compare the images obtained in 100 patients undergoing elective coronary angiography for coronary heart disease, with a portable X-ray imaging system (OEC 9600 Cardiac Version) to those obtained with a traditional fixed system (Siemens Coroskop C). RESULTS: A complete concordance between the systems for lesion location, stenosis quantification, morphologic characterization, TI-MI flow and collaterals was found. CONCLUSIONS: These findings demonstrate that a portable imaging system can produce high-quality images. The feasibility of performing a complete diagnostic procedure and the routine use of the system require more specific evaluation.

Cardiac Catheterization↗

PubMed1998

Percutaneous coronary angioplasty of unprotected left main stem: a case report.

We describe the case of a 60-year-old man with unstable angina and a critical stenosis of an unprotected left main stem. The patient was also affected with oligophrenia and Paget's disease that contraindicated surgical revascularization. We performed a percutaneous transluminal coronary angioplasty in the cardiac surgery operating room, preparing a femoro-femoral cardiopulmonary bypass by means of a portable X-ray system. The final results were good and they were confirmed by an angiographic control performed three months later as well as during the six-month follow-up. Angioplasty of the unprotected left main stem is feasible and adequate technologic support can reduce the risks for the patient.

Angina, Unstable↗

PubMed1997

Influence of interleukin-1 receptor antagonist on [3H]serotonin and histamine release by rat basophilic leukemia-2H3 cells.

Mast cells located in connective tissues are a potent source of vasoactive and inflammatory mediators, such as cytokines. They accumulate in tissues in a wide variety of diseases where their function in most cases in unclear. In this report we provide evidence that rat basophilic leukemia cells (RBLC) cultured with a natural inhibitor of IL-1, interleukin-1 receptor antagonist (IL-1RA) (500 ng/ml) for 48 h, strongly inhibited the spontaneous release of serotonin (5HT) (from 25.2 to 29.9%), and histamine (from 22.50 to 43.49%), compared to untreated cells (control). When IL-IRA-treated and -untreated RBLC were stimulated with a secretagogue (anti-IgE), no difference was found in the percent of 5HT and histamine release. The present studies describe an additional biological activity of IL-1RA, inhibiting histamine and 5HT spontaneous release from RBLC cultures.

Animals↗

PubMed1997

Impact of Rantes and MCP-1 chemokines on in vivo basophilic cell recruitment in rat skin injection model and their role in modifying the protein and mRNA levels for histidine decarboxylase.

RANTES and related molecules, constitute the C-C class of chemokine supergene family and a group of cytokines produced by hematopoietic cells constitute the MCP-1 or C-X-C class. The roles of most of these chemokines are not well known, although members of the C-X-C family are inflammatory agents. Here, we report that intradermal injection of RANTES 10 ng/50 microL subcutaneously in the abdominal skin produced a strong inflammatory reaction, as evidenced by Evans blue dye, greater than FMLP (10(-6) mol/L) (approximately 57%); while MCP-1, 10 ng/50 microL was less effective than FMLP (10(-6) mol/L) (approximately 54%). Moreover, the histologic analysis of the cells stained with Toluidine blue (0.1%) were analyzed at a magnification of x40). RANTES 10 ng/50 microL and LPS produced higher numbers (142 +/- 11 and 193 +/- 21 of cells/200 mm2, respectively) of basophilic cell accumulation in the skin injection sites compared with FMLP (10(-6) mol/L) (127 +/- 14/200 mm2), while MCP-1 10 ng/50 microL was less effective (88 +/- 10/200 mm2). Electron microscopy (x13,800) studies of skin injection sites revealed that RANTES was chemoattractant for mast cells. In a Northern blot analysis from homogeneous tissue biopsy from the intradermal injection sites, RANTES was more potent than MCP-1 in increasing histidine decarboxylase (HDC) mRNA, the sole enzyme responsible for the production of histamine from histidine. Since PGD2 is formed by mast cells on cell activation, we also studied the effect of RANTES and MCP-1 on PGD2 production in inflamed tissue in vivo. RANTES (20, 10, and 5 ng) and MCP-1 (20, 10, and 5 ng) strongly stimulated PGD2, in a dose-dependent manner, with a potency rank order of RANTES (10 ng/mL) approximately two times greater than MCP-1 (10 ng/mL).

Animals↗

PubMed1997

RANTES is a pro-inflammatory chemokine and chemoattracts basophil cells to extravascular sites.

RANTES (regulated upon activation normal T expressed and secreted) is another member of the intercrine beta subfamily which acts as a selective chemoattractant for human monocytes and CD4-positive lymphocytes and increases the adherence of monocytes to endothelial cells. In this work, the effect of RANTES was studied on rat skin injection sites. Rats were intradermally injected with 50 microliters of RANTES, at different concentrations, fMet-Leu-Phe (FMLP), or LPS (positive controls) or PBS vehicle (negative control). The animals were then injected with 0.6 ml of Evans' blue in the tail vein in order to obtain a blue colour in the areas where the compounds were injected. After 4 h the rats were killed and the maximum diameter of the blue extravasation area was measured. The coloured areas were then excised and optical and electron microscopic studies were performed. In addition, in some of the excised tissue, a Northern blot analysis for histidine decarboxylase (HDC) mRNA was performed along with an estimation of the amount of histamine generated in the tissue injection sites. In these studies it was found that intradermal injections of 5, 2.5, and 1.25 x 10(-5) M RANTES produced a strong inflammatory response with the accumulation of a great number of basophil cells compared with the PBS (50 microliters) negative control, or FMLP (10(-6) M/50 microliters) or LPS (10 ng/50 microliters) positive control, after 4 h. Moreover, 5, 2.5, 1.25 x 10(-5) M RANTES produced a dose-response stimulation of HDC mRNA in the tissues of skin injection sites. The increasing number of basophils in the RANTES inflamed tissues led to augmentation of histamine content, compared with the PBS control. In conclusion, the pro-inflammatory chemokine RANTES stimulates the generation of HDC mRNA in skin injection sites.

Animals↗

PubMed1997

Massive infiltration of basophilic cells in inflamed tissue after injection of RANTES.

Regulated upon activation normal T expressed and secreted (RANTES) is a new inducible protein member of the human C-C branch of chemokines. RANTES is a potent monocyte and lymphocyte chemoattractant and is a mediator of inflammatory responses. In these studies we found that RANTES 10 ng/50 microl chemoattracts basophilic cells in a dose-dependent manner 4 h after an intradermal injection in rat skin sites, as revealed by optic microscopy. Moreover, in biopsy specimens from rat skin injection sites histamine release was significantly higher (P < 0.05) than in controls (PBS 50 microl) after 4 h from RANTES treatment. The presence of basophilic cells in rat skin injection sites after RANTES-treatment was also confirmed by electron microscopy studies. In addition, histidine decarboxylase (HDC) mRNA was increased in rat skin sites injected with RANTES compared to sites injected with PBS (controls). Our report describes additional biological activities for RANTES, suggesting that this human chemoattractant protein may play a fundamental role in histamine and HDC generation, along with basophilic cell recruitment.

Animals↗

PubMed1997

Infra-red laser irradiation enhances interleukin-1 receptor antagonist, increases 3H-thymidine incorporation and the release of [3H]arachidonic acid in human monocytes.

The effect of infra-red laser irradiation has been experimented on various biological systems and particularly in human tissues, in vitro as well as in vivo. In order to examine the influence of laser irradiation on cells of the monocytic lineage we have irradiated human peripheral blood mononuclear cells with an infra-red laser at a wavelength of 904 nm, at 2000 Hz frequency and 15 mW for 2 min. Here, we report that laser irradiation for 2 min. at different preincubation times (T = 0 and T = 30 min) enhances LPS (10 micrograms/ml or PHA (10 micrograms/ml, suboptimal concentration)-stimulated monocytes by modifying cell proliferation, as judged by [3H] thymidine incorporation. IL-1 receptor antagonist (IL-1ra) along with an increased release of [3H] Arachidonic acid production, is also influenced by laser irradiated monocytes when treated for 2 min after 1 h incubation. IL-1RA production increased 4-5 fold after laser irradiation, while 3H-arachidonic acid incorporated from PMA-stimulated cells increased and the effect was significant at T = 0 and T = 30 min; while at T = 1 h the effect was negligible. These results may provide new information regarding the effect of laser irradiation on the immune system.

Arachidonic Acid↗

PubMed1997

Augmentation of monocyte chemotactic protein-1 and mRNA transcript in chronic inflammatory states induced by potassium permanganate (KMnO4) in vivo.

Monocyte chemotactic protein-1 (MCP-1) is a proinflammatory cytokine that attracts and activates specific types of leucocytes. The purpose of this work was to analyse the generation of MCP-1 and mRNA transcript in a model of chronic inflammation using a granulomatous tissue induced by potassium permanganate (KMnO4; water soluble crystals). The data presented here shows that MCP-1 is generated in granuloma tissue and its level was strongly increased by i.p. injections of lipopolysaccharide (LPS) and inhibited in rats treated with injections of dexamethasone, 18 hr before the animals were killed. In histological studies LPS and dexamethasone increased and decreased, respectively, the recruitment of mononuclear cells in the granuloma tissue compared with the control granulomas from phosphate-buffered saline (PBS)-treated animals. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used for mRNA extraction and cDNA synthesis. mRNA MCP-1 was significantly produced in the granuloma tissue of untreated animals, an effect increased by LPS and inhibited by dexamethasone, compared with the controls. Moreover, MCP-1 protein was found in the supernatant from homogenized granuloma tissues and the levels of MCP-1 were higher in the LPS-treated animals, while they were lower in the dexamethasone group, compared with the granulomas from the PBS-treated groups (control). The generation of MCP-1 was also found in minced granuloma tissue incubated for 18 hr (overnight) from treated (LPS or dexamethasone) and untreated (PBS) rats. When LPS was added in vitro for 18 hr to the controls and treated animals the production of MCP-1 was further increased except in the dexamethasone group (P > 0.05). Analysing blood serum from LPS, dexamethasone or PBS-treated rats, we found that MCP-1 was also present. The level was higher in the LPS group and lower in the dexamethasone group, compared with the control (PBS). In these studies we show for the first time that MCP-1 transcript and translation is generated in chronic experimental inflammatory tissue, an effect inhibited by dexamethasone.

Animals↗

PubMed1997

Monocyte chemotactic protein-1 is a proinflammatory chemokine in rat skin injection sites and chemoattracts basophilic granular cells.

Chemokines may control mast cell infiltrates found in many inflammatory diseases. These cells act through at least two main functions: migration and degranulation. Here we show that human recombinant monocyte chemotactic protein (MCP)-1 (10 ng/50 microliters) induces, after 4 h, an inflammatory vascular permeability and cellular extravasation reaction, determined by Evan's blue dye (1% in saline) injected into the tail vein of the rat, when injected intradermally in the rat skin. The blue color accumulating at the sites of injection provides evidence of vascular permeability and cellular extravasation. The colored areas of the skin were then enucleated and immersed in a fixative solution. Slides were prepared with sections of tissue colored with toluldine blue and analyzed under an optical microscope. A significant number of basophilic cells migrated to the injected area where MCP-1 (10 ng/50 microliters) was used compared to the control PBS treatment. Cell recruitment was slightly less than N-formyl-methionine-leucyl-phenylalanine (used at 10(-6) M/50 microliters). Electron microscopy studies confirmed the presence of basophilic granular cells where MCP-1 was intradermally injected. After preparation of a histidine decarboxylase (HDC) probe, a Northern blot analysis was determined for HDC mRNA in the enucleated tissue injected with MCP-1 (10 ng/50 microliters). Steady-state levels of HDC mRNA levels were induced after 4 h. These results were confirmed by the higher amount of histamine release, compared to the control PBS, in the enucleated tissue from the MCP-1 injection sites. Our results suggest that MCP-1 could play a significant role in diseases characterized by basophilic cell accumulation and migration to sites of tissue damage. Moreover, we show for the first time that MCP-1 is a pro-inflammatory chemokine that induces basophilic cell migration in rat skin injection sites.

Animals↗