Polymorphonuclear Leukocyte Chemotaxis Research Articles

Reactive nitrogen species modulate the effects of rhein, an active component of senna laxatives, on human epithelium in vitro.

Senna laxatives are used worldwide. However, their misuse can lead to chronic mucosal inflammation with the accumulation of pigment-laden leukocytes and may cause colon cells to undergo apoptosis. This study explores the mechanisms by which rhein, an active component of senna, acts on a human intestinal cell line to induce ion secretion, apoptosis, and indirect chemotaxis of polymorphonuclear leukocytes. Human colonic adenocarcinoma (CaCo-2) monolayer cells, in the presence or in the absence of rhein, were used to monitor the production of reactive nitrogen species using the Griess reaction. Modified Ussing chambers were used to study electrolyte secretion. The capacity to recruit human polymorphonuclear leukocytes was evaluated using masked well chemotaxis chambers. Rhein-induced apoptosis was investigated by counting apoptotic nuclei stained with Hoechst 33258 dye. Rhein caused a dose-dependent increase in short-circuit current that was abolished in chloride-free bathing buffer or by preincubating with 100 micromol/L NG-nitro-L-arginine (L-NAME) methyl ester. The concentration that maximally stimulated intestinal secretion, 50 micromol/L rhein, induced nitrate production. Supernatants obtained from CaCo-2 cultures after incubation with 50 micromol/L rhein stimulated a time-dependent polymorphonuclear leukocytes chemotaxis that was significantly decreased with 100 micromol/L L-NAME, whereas rhein per se was not active. Neutralizing antibodies anti-interleukin-8 (IL-8) and anti-ENA78 also inhibited chemotaxis. Overnight rhein incubation produced an increased number of apoptotic cells in the culture supernatant that was significantly decreased by preincubation with 100 micromol/L L-NAME. Light-degraded rhein had no effects on CaCo-2 monolayers. The integrity of rhein is crucial to generating nitric oxide, which mediates, with different time courses, ion secretion, chemotaxis, and apoptosis of human-derived cells.

Cleavage of the Fifth Component of Human Complement and Release of a Split Product with C5a-like Activity by Crystalline Silica through Free Radical Generation and Kallikrein Activation

The effects of the same form of crystalline silica variously modified were compared to investigate the mechanisms by which silica activates C5 molecules. After incubation in human plasma, silica generated C5a-type fragments that stimulated polymorphonuclear leukocyte chemotaxis. This activity was totally abolished when plasma, adsorbed with antiserum against C5a or thermally inactivated, was used. Pretreatment of plasma with deferoxamine, 1,3 dimethyl-2-thiourea, or aprotinin markedly inhibited or totally abolished C5 activation. Finally, a significant increase in kallikrein activity was detected after incubation of silica particles in plasma. The results seem to indicate that the activation of C5 by crystalline silica occurs through a complex mechanism: the redox-active iron possibly present at the silica surface catalyzes, via Haber–Weiss cycles, the production of hydroxyl radicals, which in turn convert native C5 to an oxidized C5-like form. This product is then cleaved by kallikrein, activated by the same silica particles, yielding oxidized C5a with the same functional properties as C5a. The different types of the same form of silica exhibited different reactivity. Two separate properties of the dusts seem to contribute to C5 activation: the potential to release hydroxyl radicals and the extent of C5 adsorption at the surface. The degree of surface hydrophobicity/hydrophilicity appeared sufficient to explain the different responses.

Pharmacological and clinical properties of levocabastine hydrochloride (eye drop and nasal spray), a selective H1 antagonist

Levocabastine is a selective histamine H1-receptor antagonist exerting inhibitory effects on the release of chemical mediators from mast cells and on the chemotaxis of polymorphonuclear leukocytes and eosinophils. Both histamine and antigens induced conjunctivitis was inhibited by levocabastine in several allergy models. Levocabastine moderately inhibited histamine-release from guinea pig conjunctive induced by antigen-antibody reactions and prevented an increase in the vascular permeability of the conjunctive elicited by both histamine and antigen instillation. Symptoms of allergic rhinitis, which were induced by histamine, substance P and antigen, were also reduced by levocabastine. Levocabastine prevented an increase in the vascular permeability of nasal mucosa elicited by instillation of these three inducers. Furthermore, levocabastine has shown a large difference between the antiallergic dose and other non-specific pharmacological effective dose than that with other antiallergic drugs. The non-specific pharmacological effect of levocabastine reveals only blepharoptosis. With these pharmacological effects and topical usage, levocabastine was shown to be useful for allergic conjunctive and rhinitis in both seasonal and perennial clinical use.

Inhibition of IL-8-mediated MAPK activation in human neutrophils by beta1 integrin ligands.

Chemokine and integrin receptors must work in concert when circulating leukocytes mobilize toward a site of tissue inflammation or infection. In a previous study, we reported that ligation of the alpha5beta1 integrin with a 120-kDa cell-binding fibronectin fragment (120-kDa FN) in suspensions of human polymorphonuclear leukocytes (PMNLs) inhibited chemotaxis toward the chemokine called interleukin-8 (IL-8). Binding of chemokines to their receptors on leukocytes leads to the activation of heterotrimeric G proteins that initiate multiple signaling cascades, including p38 and p42/p44 mitogen-activated protein kinase (MAPK) pathways. In the present study, we examine the potential interaction of beta1 integrin ligation on chemokine-mediated MAPK signaling in human PMNLs. We demonstrate that blockade of the p42/p44 MAPK signaling pathway by the inhibitor PD98059 suppresses IL-8-mediated PMNL chemotaxis. Furthermore, when PMNLs are pretreated with 120-kDa FN or an activating antibody to beta1 integrins (TS2/16), IL-8-mediated phosphorylation of p42/p44 MAPK is also inhibited. In contrast, pretreating PMNL with a specific ligand (laminin-1) for the alpha6beta1 integrin does not suppress IL-8-mediated phosphorylation of p42/p44 MAPK. These observations demonstrate a desensitization of IL-8-mediated p42/p44 MAPK signaling in response to ligation of the alpha5beta1 integrin in PMNL. Also, they suggest an interplay between integrin and chemokine signaling during PMNL migration through the extracellular matrix.

Clindamycin/benzoyl peroxide gel: a review of its use in the management of acne.

Clindamycin/benzoyl peroxide gel has demonstrated clinical efficacy in the treatment of acne vulgaris through both antibacterial and anti-inflammatory means. Benzoyl peroxide may exert its antibacterial activity by the interaction of oxidized intermediates with elements of bacterial cells. Clindamycin inhibits bacterial protein synthesis by binding to the 50S ribosomal subunits causing inhibition of peptide-bond formation. Benzoyl peroxide decreases inflammatory damage by inhibiting the release of reactive oxygen species from polymorphonuclear leukocytes (PMNs) through the killing of PMNs. Clindamycin suppresses the complement-derived chemotaxis of polymorphonuclear leukocytes in vitro, thereby reducing the potential for inflammation. Several well designed clinical trials have demonstrated that twice-daily application of clindamycin 1%/benzoyl peroxide 5% gel for 10 to 16 weeks was more effective in reducing the number of inflammatory lesions than benzoyl peroxide 5%, clindamycin 1% or vehicle in patients with mild to moderately severe acne. Two studies also showed clindamycin/benzoyl peroxide to be more effective than benzoyl peroxide, clindamycin or vehicle in reducing total lesions, and one study showed clindamycin/benzoyl peroxide to be significantly more efficacious than clindamycin or vehicle in reducing the number of noninflammatory lesions. Moreover, in two trials, physician-rated mean global improvement scores, as well as patient-rated scores in one of those trials, were significantly greater in the clindamycin/benzoyl peroxide group than in the benzoyl peroxide, clindamycin or vehicle groups. In another study, clindamycin/benzoyl peroxide was as efficacious as benzoyl peroxide/erythromycin in the reduction of inflammatory and noninflammatory lesions and in raising mean global improvement scores, but was significantly more effective than benzoyl peroxide in the reduction of inflammatory lesions and in increasing both physician- and patient-assessed global improvement scores. Clindamycin/benzoyl peroxide gel applied twice daily was well tolerated in clinical trials in patients with acne, and has a tolerability profile similar to that of benzoyl peroxide alone. The most common adverse events were dry skin, peeling, erythema and rash; however, adverse event-caused treatment discontinuation rates for patients using clindamycin/benzoyl peroxide were low, ranging from 0 to 0.8%. Clindamycin/benzoyl peroxide gel has demonstrated efficacy and good overall tolerability in several well designed clinical studies in the topical treatment of patients with mild to moderately severe acne vulgaris. Clindamycin/benzoyl peroxide was more effective than benzoyl peroxide, clindamycin or vehicle, and similar in efficacy to benzoyl peroxide/erythromycin in the reduction of inflammatory lesions and in raising physician- and patient-assessed mean global improvement scores. It may be useful in treating patients with acne caused by resistant strains of Propionibacterium acnes. Clindamycin/benzoyl peroxide gel is an effective topical agent in the treatment of patients with mild to moderately severe acne. It is a suitable alternative for patients who are currently using topical antibacterials either alone or in conjunction with other topical anti-acne agents or systemic antibacterials.

Increased neutrophil motility by beta-glucan in the absence of chemoattractant.

Systemic candidasis is a life-threatening complication of antibiotic and immunosuppressive therapies and can alter host defense mechanisms through pathways that are poorly understood. Promotion of polymorphonuclear leukocyte (PMN) chemotaxis by beta-glucan towards fMLP or IL-8 gradients demonstrates a fundamental effect on host defenses by pathogenic fungi. The aim of the present study was to determine whether recognition of beta-glucan is sufficient to alter PMN motility in the absence of agonists of G-coupled protein chemotactic receptors. Present findings demonstrate a profound increase in PMN motility by beta-glucan supplementation of a fibronectin substratum in an underagarose migration assay. Motility on beta-glucan included a 3-fold increase in distance of migration, as well as a 5-fold increase in the number of PMNs recruited into the motile phase as compared to motility on fibronectin alone. This promotion of motility is determined by the beta2 integrin complement receptor 3 (CR3) (CD11b/CD18) rather than the beta1 integrin very late antigen 3 (VLA-3), which mediates chemotaxis on beta-glucan-supplemented matrix towards fMLP. PMN motility on beta-glucan-supplemented fibronectin was selectively decreased by inhibitors of pp60 src and ras, whereas motility was promoted by inhibition of p38-MAPK. No effect of these inhibitors was seen on PMNs migrating on fibronectin alone. Migration on beta-glucan-supplemented fibronectin, but not on fibronectin alone, was negatively regulated by protein kinase C (PKC) or cAMP activation. These findings indicate that beta-glucan is sufficient to alter the migratory capacity of PMN in the absence of costimulation by fMLP. Enhanced PMN migration on beta-glucan is mediated through specific integrins and second messenger pathways that are distinct from those utilized by PMNs migrating in the absence of beta-glucan.

Blockade of alpha 5 beta 1 integrins reverses the inhibitory effect of tenascin on chemotaxis of human monocytes and polymorphonuclear leukocytes through three-dimensional gels of extracellular matrix proteins.

Tenascin is an extracellular matrix protein found in adults in T cell-dependent areas of lymphoid tissues, sites of inflammation, and tumors. We report here that it inhibited chemotaxis of chemoattractant-stimulated human monocytes and chemoattractant-stimulated polymorphonuclear leukocytes (PMN) through three-dimensional gels composed of collagen I or Matrigel, and chemotaxis of leukotriene B4-stimulated PMN through fibrin gels. The inhibitory effect of tenascin on monocyte or PMN chemotaxis through these matrices was reversed by Abs directed against alpha5beta1 integrins or by a peptide (GRGDSP) that binds to beta1 integrins. Tenascin did not affect leukotriene B4- or fMLP-stimulated expression of beta1 or beta2 integrins, but did exert a small inhibitory effect on PMN adhesion and closeness of apposition to fibrin(ogen)-containing surfaces. Thus, alpha5beta1 integrins mediate the inhibitory effect of tenascin on monocyte and PMN chemotaxis, without promoting close apposition between these leukocytes and surfaces coated with tenascin alone or with tenascin bound to other matrix proteins. This contrasts with the role played by alpha5beta1 integrins in promoting close apposition between fMLP-stimulated PMN and fibrin containing surfaces, thereby inhibiting chemotaxis of fMLP-stimulated PMN through fibrin gels. Thus, chemoattractants and matrix proteins regulate chemotaxis of phagocytic leukocytes by at least two different mechanisms: one in which specific chemoattractants promote very tight adhesion of leukocytes to specific matrix proteins and another in which specific matrix proteins signal cessation of migration without markedly affecting strength of leukocyte adhesion.

Glucose-modified proteins modulate essential functions and apoptosis of polymorphonuclear leukocytes.

Any modulation of the activity of polymorphonuclear leukocytes (PMNL) is a potential cause of the altered immune response in uremia. Because the level of glycation products is elevated in uremic sera and peritoneal effluents, the effect of glycated proteins on essential functions and on apoptosis of PMNL was investigated. Proteins from sera of healthy donors were incubated with and without glucose. The extent of early glycation was monitored by boronate chromatography and the fructosamine assay. The formation of late glycation products was assessed by fluorescence spectroscopy and Western blotting that used a specific antibody for imidazolone, a late glycation product. With the addition of aminoguanidine, a compound that inhibits the formation of late but not of early glycation products, protein samples with early glycation only were obtained. Glucose-modified proteins increased chemotaxis and activation of the 2-deoxy-D-glucose uptake of PMNL obtained from healthy donors, compared with those of unmodified proteins. PMNL apoptosis, assessed by morphologic changes, by detecting DNA strand breaks, and by measurement of the caspase 3 activity, was increased in the presence of glucose-modified serum proteins. It was found that the formation of late glycation products is necessary for the effect on PMNL chemotaxis. In contrast, early glycation of proteins is responsible for the increase of glucose uptake and apoptosis. It was concluded that the accumulation of glycated proteins in uremic sera and peritoneal fluid may contribute to the diminished immune function observed in uremia, by modulation of essential PMNL functions and acceleration of PMNL apoptosis.

Expression of aminopeptidase N in human endometrium and regulation of its activity by estrogen

Objective: To determine whether aminopeptidase N (APN) regulates the cycle-dependent bioavailability of interleukin-8 (IL-8) in the endometrium. Design: Prospective study. Setting: University medical center. Patient(s): Women without endometrial pathology from the proliferative (n = 25) or secretory (n = 18) phase of the menstrual cycle. Intervention(s): We first immunolocalized APN in the endometrium using an anti-APN antibody. We then determined the regulation of APN kinetic activity by sex steroids in endometrial stromal cell cultures. Main Outcome Measure(s): Expression of APN in human endometrium throughout the menstrual cycle. Regulation of APN activity by estradiol and progesterone in cultured endometrial stromal cells. Result(s): Immunohistochemistry of endometrial sections revealed staining of endometrial stroma throughout the menstrual cycle. There was no detectable staining in glandular cells. The expression of APN as detected by immunohistochemistry was significantly lower in the early proliferative phase. In cultured cells, estradiol inhibited APN activity in a concentration-dependent manner. Progesterone did not have a significant effect. Conclusion(s): Stromal localization of APN in endometrium may explain the epithelial rather than stromal presence of IL-8 in vivo. Decreased expression of APN may increase IL-8 bioavailability thus contributing to angiogenesis and polymorphonuclear leukocyte chemotaxis in early proliferative phase.

Monocyte-macrophage system and polymorphonuclear leukocytes in workers exposed to low levels of metallic mercury

Our previous research (Soleo L, Vacca A, Vimercati L et al. Occup Environ Med 1997;54:437–442) showed a reduction in tumor necrosis factor-α (TNF-α) serum levels in workers with prolonged exposure to low doses of inorganic mercury, suggesting an in vivo functional defect of the monocyte-macrophage system. On this basis, here we wondered whether workers exposed to lower doses of metallic mercury displayed possible changes in the monocyte-macrophage system. In this particular cohort of workers, we also sought for the effects of the exposure on the polymorphonuclear leukocytes (PMNL) chemotaxis. The monocyte-macrophage system and the natural killer (NK) cells were examined in 19 exposed workers and in 25 unexposed workers, as the control group (controls). Specifically, the circulating monocyte-macrophage cells and their CD13, CD15 and CD33 subsets, serum cytokines (IL-8, GM-CSF and TNF-α) and the NK cells were analyzed. In seven exposed and seven controls randomly chosen workers the PMNL chemotaxis was also assessed. The selected indicator of mercury exposure were the levels of mercury in the urine (U-Hg), that was significantly higher in exposed workers than the controls (9.7±5.5 μg/l and 2.4±1.2 μg/l, respectively). None of the exposed workers had shown signs of either acute or chronic inorganic mercury toxicity or any form of hypersensitivity. Several immunological variables tested, monocyte-macrophage cells and their subsets, NK cells and serum cytokines overlapped between the exposed and the control workers. When the workers were considered as a whole (exposed plus controls), no correlation was found between current U-Hg and all immunological parameters. However, when exposed workers were studied separately, an inverse correlation was disclosed between cumulative U-Hg and cells (as percentage) expressing the CD13 ( r=−0.599; P=0.007) and CD15 ( r=−0.614; P=0.005) molecules, and NK cells ( r=−0.455; P=0.05). Moreover, a significant impairment in the PMNL chemotaxis ( t=3.70; P=0.003) was observed in the exposed workers. The results of our study suggest that the exposure to very low levels of metallic mercury led to subtle impairment of circulating monocyte and NK cells (as percentages) according to the increase in U-Hg levels, as well as of the PMNL chemotactic function in this particular group of workers, even though they remain clinically asymptomatic. Therefore, we suggest that impairment of these parameters provide a sensitive indicator of metallic mercury and other chemical contaminants present in the environment.

Effects of macrolides on chemotaxis and phagocytosis of polymorphonuclear leukocytes in experimental rabbit infection models

Effects of macrolides on chemotaxis and phagocytosis of polymorphonuclear leukocytes in experimental rabbit infection models

Ex vivo and in vitro effect of human immunodeficiency virus protease inhibitors on neutrophil apoptosis.

Polymorphonuclear leukocytes (PMNL) from human immunodeficiency virus (HIV)-infected patients exhibit accelerated apoptosis and impaired functional activity. HIV protease inhibitor-based therapy produces improvements in both acquired and innate immune responses. Ex vivo and in vitro effects of HIV protease inhibitors on apoptosis and chemotaxis of PMNL were evaluated. After therapy, there was a rapid and significant decrease of PMNL apoptosis, which correlated with increased chemotactic function. These findings were found both in patients with immunological and virological response and in control subjects who showed an increase in CD4(+) T cell counts but no concomitant decline in HIV load. After in vitro treatment with ritonavir or indinavir, apoptosis of both HIV-infected and -uninfected PMNL markedly decreased and correlated with significant enhancement of chemotaxis. These results suggest that HIV protease inhibitors may improve the PMNL function by reducing the apoptosis rate and that this effect may, at least in part, be independent of their antiviral activity.

Random locomotion and chemotaxis of human blood polymorphonuclear leukocytes from a patient with Leukocyte Adhesion Deficiency‐1: Normal displacement in close quarters via chimneying

Random locomotion and chemotaxis of human blood polymorphonuclear leukocytes from a patient with Leukocyte Adhesion Deficiency‐1: Normal displacement in close quarters via chimneying

IN VITRO CLEAVAGE BY ASBESTOS FIBERS OF THE FIFTH COMPONENT OF HUMAN COMPLEMENT THROUGH FREE-RADICAL GENERATION AND KALLIKREIN ACTIVATION

Chrysotile and crocidolite fibers incubated in normal human plasma (NHP) generated from the C5 component of complement C5a-type fragments that stimulated polymorphonuclear leukocyte (PMN) chemotaxis. Absorption of NHP with antiserum against C5a totally abolished neutrophil chemotactic activity. Asbestos fibers also produced C5a small peptides in the presence of ethylene glycol bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA) but not ethylene diamine tetraacetic acid (EDTA). Activation of C5 was significantly inhibited when asbestos fibers were pretreated with iron chelators such as sodium dithionite (DTN), deferoxamine (DFX), or ascorbate (AA). Concentration-related inhibition of C5 activation was also observed when asbestos fibers were added concurrently to plasma in the presence of DFX, 1,3-dimethyl-2-thiourea (DMTU), a strong hydroxyl scavenger, or aprotinin (APR), a specific protease inhibitor. Further, chrysotile and crocidolite significantly increased plasma kallikrein activity. Data demonstrate that asbestos-induced C5 activation plays a role in inflammatory reactions characteristic of asbestosis through mechanisms involving iron ions, hydroxyl radicals, and oxidized C5-like fragments. The ferrous ions present at the asbestos fiber surface trigger this activation and catalyze, via Fenton reaction, the production of hydroxyl radicals, which in turn convert native C5 to an oxidized C5-like form. This product is then cleaved by kallikrein, activated by the same asbestos fibers, yielding an oxidized C5a with the same functional properties as C5a.

DIFFERENCES IN THE MICROTUBULE ORGANIZATION BETWEEN NORMAL AND CML GRANULOCYTES AFTER STIMULATION WITH CHEMOTACTIC PEPTIDE

Chemotaxis of polymorphonuclear leukocytes (PMNL) from chronic myeloid leukemia (CML) patients followed in a gradient of a chemotactic peptide n-formyl-methionyl-leucyl-phenylalanine (fMLP) is consistently defective in all the phases of the disease. Chemoattractant-induced polymerization of cytoskeletal proteins (actin and tubulin) plays a major role in regulation of cell shape and cellular motility. To study the role of microtubules in defective chemotaxis, we have compared fMLP-induced alterations in organization of microtubules in PMNL from CML patients with those from normal subjects by laser confocal microscopy. Our analysis shows differences in microtubule organization between normal and CML PMNL and suggests that both nucleation of new microtubule and elongation of pre-existing microtubules are essential for PMNL chemotaxis.

Neutrophil chemotaxis and random migration in preterm and term infants with sepsis.

The aim of this study was to evaluate neutrophil chemotaxis and random migration in healthy newborn infants and septic neonates with similar gestational and postnatal age. Possible relationships between chemotactic activity, random migration, causative microorganisms, and clinical course of septic infants were also investigated. The neutrophil chemotaxis and random migration was evaluated in 24 healthy newborn babies and 34 septic neonates and 20 healthy adults by modified Boyden technique. The mean neutrophil chemotaxis of healthy preterm-term infants and adults were similar (66.6 +/- 18.9, 64.4 +/- 19.9, and 74.7 +/- 17 microm, respectively). The mean neutrophil random migration of healthy term infants was not different than that of adults. But the mean neutrophil random migration of healthy preterm infants was lower than that of adults (36.9 +/- 13.7 and 43.5 +/- 1 1.8 microm, respectively) (p = 0.03). The mean neutrophil chemotaxis and random migration septic term infants were not different from the value of healthy term infants (p > 0.05). Although the mean random migration of septic and preterm infants were similar (p > 0.05), the mean neutrophil chemotaxis of septic preterm infants was lower than the value of healthy preterm infants (p = 0.04). Not only mean neutrophil chemotaxis of septic preterm and term infants were significantly lower than that of adults (p = 0.002 and p = 0.006, respectively), but also neutrophil random migration of septic preterm and term infants were significantly lower than that of adults (p = 0.001 and p = 0.005, respectively). There was no relationship between the nature of causative microorganism and neutrophil random migration or chemotactic activity. Polymorphonuclear leukocytes chemotaxis was significantly lower in preterm with sepsis compared with healthy preterm-term infants and adults. These findings may indicate deterioration in neutrophil functions in premature babies under stress but more detailed studies with larger groups are needed.

Random locomotion and chemotaxis of human blood polymorphonuclear leukocytes from a patient with leukocyte adhesion deficiency-1: normal displacement in close quarters via chimneying.

The beta2 integrins are known to be important in the motile function of leukocytes in general and in the adhesive response to inflammatory stimuli in particular. In the current study, under direct microscopic observation with concomitant time-lapse video recording, we examined the locomotion of human blood PMN from a patient with Leukocyte Adhesion Deficiency-1 (LAD), a disorder in which beta2 integrins on the cell surface are markedly deficient in number or function. In thin slide preparations such that the leukocytes were somewhat compressed between slide and cover slip, PMNLAD exhibited normal random locomotion and chemotaxis, apparently by using the opposing surfaces to generate the force for locomotion (chimneying). In thicker preparations, an adherence deficit was evident, but chemotaxis still occurred, even by PMNLAD anticoagulated in EDTA. Consistent with the paucity of beta2 integrins on the surface of the PMNLAD was their failure to aggregate in the presence of antibodies to beta2 integrins, even when they had been brought together by chemotaxis. We relate these findings to the reported independence from integrins of PMN in the lung vasculature in LAD, as well as in certain experimental conditions.

Rose hip inhibits chemotaxis and chemiluminescence of human peripheral blood neutrophils in vitro and reduces certain inflammatory parameters in vivo

The objective of this study was to investigate the leucocyte-related antiinflammatory properties of rose hip. The effect of rose hip on a number of inflammatory parameters was evaluated using the following models: (1) The effect of rose hip extract on chemotaxis and chemiluminescence of peripheral blood polymorphonuclear leucocytes (PMNs) from healthy subjects in vitro; (2) The effect of rose hip administered to healthy subjects on serum levels of creatinine and C-reactive protein and on chemotaxis and chemiluminescence of peripheral blood PMNs. Rose hip extract at concentrations higher than 500 micro/m1 inhibited the chemotaxis and chemiluminescence of peripheral blood polymorphonuclear leucocytes in vitro. Daily intake of rose hip powder at doses of 45 grams or lower by healthy subjects resulted in reduced chemotaxis of peripheral blood PMNs and reduced the level of serum creatinine and acute phase protein CRP. These results indicate that rose hip possesses antiinflammatory properties and might be used as a replacement or supplement for conventional drug therapies in some inflammatory diseases such as arthritis.

Transcriptional regulation of 15-lipoxygenase in human coloretal carcinoma cells by histone deacetylase inhibitors

Anti-inflammatory effects of the 15-lipoxygenase (15-LO) derivatives lipoxin A4 (LXA4) and 15-S-hydroxyeicosatetraenoic acid (15-S-HETE) have been documented in many experimental models of acute inflammation. However, the expression levels of 15-LO and its products in human renal diseases remain unknown. This study investigated the expression levels of LXA4, leukotriene B4 (LTB4), and 15-LO in leukocytes and glomeruli obtained from 22 children with acute poststreptococcal glomerulonephritis (APSGN), and determined the modulatory effects of both 15-S-HETE and LXA4 on LTB4 synthesis in leukocytes and LTB4-evoked chemotaxis of polymorphonuclear leukocytes (PMNs) obtained from children during the first 3 days after onset of APSGN. Expression levels of both LXA4 and 15-LO in leukocytes and glomeruli were up-regulated during the acute phase of disease, further peaking between days 10 and 14, and remained increased after 6 to 8 weeks of APSGN onset. In contrast, blood and urinary levels of LTB4 as well as the number of glomerular PMNs peaked during the acute phase of disease and then decreased during the resolution phase. Administration of both 15-S-HETE and LXA4 in vitro inhibited LTB4-induced chemotaxis of PMNs and production of LTB4 from leukocytes obtained from patients with APSGN. The current study provides further support for an anti-inflammatory role for 15-LO products in human nephritis through both antagonism and inhibition of leukotriene synthesis and its biological activity.

Neutrophil chemotaxis on silicone and polyurethane surfaces.

Silicone vascular catheters have a greater risk of infection and produce greater inflammation in vivo and greater complement activation in vitro than other vascular catheter polymer materials. This study investigated whether polymorphonuclear leukocyte (PMNL) chemotaxis under agarose on silicone surfaces is different than on polyurethane (PU). Glass slides were coated with silicone and PU by use of a constant-speed dipping apparatus. Chemotaxis (3 h) in response to (10-7 mL) FMLP, zymosan-activated serum, and fresh serum (100%) was greater on silicone than on PU (P<.05). Polyclonal antibody to C5a blocked >50% of the movement toward serum (P<.05). Serum in the PMNL well significantly decreased chemotaxis toward FMLP on silicone (P<.05) but not on PU. These findings suggest that excessive complement activation by silicone may interfere with chemotaxis, but further work is necessary to determine whether this is relevant to an increased risk of catheter-related infection.