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PubMed1999

Inhibition of a membrane complement regulatory protein by a monoclonal antibody induces acute lethal shock in rats primed with lipopolysaccharide.

Rats pretreated with traces of LPS developed acute fatal shock syndrome after i.v. administration of a mAb that inhibits the function of a membrane complement regulatory molecule. Such a shock was not observed after the administration of large amounts of LPS instead of the mAb following LPS pretreatment. The lethal response did not occur in rats depleted of either leukocytes or complement, and a C5a receptor antagonist was found to inhibit the reaction. Furthermore, LPS-treated rats did not suffer fatal shock following the injection of cobra venom factor, which activates complement in the fluid phase so extensively as to exhaust complement capacity. Therefore, complement activation on cell membranes is a requirement for this type of acute reaction.

Acute Disease↗
PubMed1996

Effects of theophylline and rolipram on leukotriene C4 (LTC4) synthesis and chemotaxis of human eosinophils from normal and atopic subjects.

1. The effects of the non-selective phosphodiesterase (PDE) inhibitor theophylline and the selective PDE4 inhibitor rolipram on leukotriene C4 (LTC4) synthesis and chemotaxis of complement 5a (C5a)- and platelet-activating factor (PAF)-stimulated human eosinophils obtained from normal and atopic donors were investigated. 2. Eosinophils were purified from peripheral venous blood of normal and atopic subjects by an immunomagnetic procedure to a purity > 99%. Eosinophils were stimulated with PAF (0.1 microM) or C5a 0.1 microM for 15 min and LTC4 was measured by radioimmunoassay (RIA). Eosinophil chemotaxis in response to PAF and C5a was assessed with 48-well microchambers (Boyden). 3. Under these conditions substantial amounts of LTC4 (about 300-1000 pg per 10(6) cells) were only detectable in the presence of indomethacin (0.1-10 microM). To explain this finding it was hypothesized that indomethacin reversed the inhibition of LTC4 synthesis by endogenously synthesized prostaglandins, in particular prostaglandin E2 (PGE2). In fact, eosinophils release 23 pg PGE2 per 10(6) cells following PAF stimulation; this PGE2 synthesis was completely inhibited by indomethacin and readdition of PGE2 inhibited eosinophil LTC4 synthesis (IC50 = 3 nM). The following experiments were performed in the presence of 10 microM indomethacin. 4. Theophylline (IC50 approximately 50 microM) and rolipram (IC50 approximately 0.03-0.2 microM) suppressed PAF- and C5a-stimulated LTC4 synthesis. This PDE inhibitor-induced suppression of LTC4 generation is mediated by activation of protein kinase A, since it was reversed by the protein kinase A inhibitor Rp-8-Br-cyclic AMPS. In addition, exogenous arachidonic acid concentration-dependently (0.3 microM-3 microM) reversed the inhibition of LTC4 synthesis by the PDE inhibitors, indicating that theophylline and rolipram suppress the mobilization of arachidonic acid. The beta 2-adrenoceptor agonist salbutamol inhibited eosinophil LTC4 synthesis (IC50 = 0.08 microM). The combination of salbutamol with theophylline (10 microM) or rolipram (3 nM) appeared to be additive. 5. Theophylline (IC50 approximately 40 microM), rolipram (IC50 approximately 0.02 microM [C5a], approximately 0.6 microM [PAF]) and PGE2 (IC50 approximately 3 nM) inhibited C5a- and PAF-stimulated eosinophil chemotaxis. The combination of PGE2 with theophylline resulted in an additive effect. 6. Both C5a- and PAF-stimulated eosinophil chemotaxis and LTC4 generation were significantly elevated in eosinophils from atopic individuals compared to normal subjects. However, eosinophils from normal and atopic individuals were not different with respect to their total cyclic AMP-PDE and PDE4 isoenzyme activities as well as the potencies of theophylline and rolipram to suppress LTC4 generation and chemotaxis.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2003

Chemotaxis of blood neutrophils from patients with primary ciliary dyskinesia.

Primary ciliary dyskinesia is characterized by chronic upper and lower respiratory infections which are caused by the grossly impaired ciliary transport. Since the cilia and neutrophils both utilize microtubular system for their movement, it has been speculated that neutrophil motility such as chemotaxis might be impaired in patients with primary ciliary dyskinesia. Neutrophils were purified from whole blood from 16 patients with primary ciliary dyskinesia and from 15 healthy controls. Chemotactic responses of neutrophils to leukotriene B(4) (LTB(4)), complement 5a (C5a), and formylmethionylleucylphenylalanine (fMLP) were examined using the under agarose method. The chemotactic differentials in response to LTB4, C5a, and fMLP in neutrophils from the patient group were significantly lower than the corresponding values in neutrophils from the control group (p<0.05 for all comparisons). The difference in chemotactic index between the two groups was statistically significant for LTB4 and fMLP (p<0.05 for both comparisons), but not for C5a (p=0.20). Neutrophils from patients with primary ciliary dyskinesia showed a decreased chemotactic response as compared with those from normal subjects. It is concluded that the increased frequency of respiratory tract infection in patients with primary ciliary dyskinesia is possibly due to the defective directional migration of neutrophils, as well as to the defective mucociliary clearance of the airways.

Adolescent↗
PubMed1982

Cellular changes in bone marrow of malaria-infected mice. III. Chemotaxis of granulocytes.

The number of bone marrow cells and their chemotactic activity was studied during malaria infection. Two days after infection of Balb/c mice with Plasmodium berghei, an increase in granulocyte number was observed in the blood. A modified Boyden chamber chemotaxis assay was employed to investigate the mechanism of granulocyte accumulation in the blood. Bone marrow cells from normal mice, from mice during a primary lethal infection and from immune mice after challenge were compared. The complement factor C5a showed chemotactic activity for bone marrow cells; a significant decrease of chemotaxis was only observed after 6 days of primary infection. Extracts of spleen, liver and infected erythrocytes lacked chemotactic activity, or caused inhibition of cell migration. Serum from mice with a 2-day primary infection contained chemotactic activity. The active component was heat labile, protease sensitive and had an estimated molecular weight of 250,000.

Animals↗
PubMed2002

Apoptosis of bovine neutrophils following diapedesis through a monolayer of endothelial and mammary epithelial cells.

In a two-chamber system, isolated blood polymorphonuclear neutrophil leukocytes (PMN) were allowed to migrate (5 h, 37degrees C) in response to bovine complement component C5a across calfskin and rat-tail type I collagen-coated micropore membranes, arterial endothelial, or mammary epithelial cell monolayer on calfskin and rat-tail collagen-coated membranes, respectively. Migration through calfskin collagen-coated membranes resulted in 14.5% +/- 3.4% apoptotic PMN, which was significantly higher than 6.6% +/- 1.2% apoptotic nonmigrated C5a-treated PMN. The addition of an endothelial or epithelial cell monolayer to collagen-coated membranes prevented apoptosis of migrated PMN. After removing the membranes, nonmigrated (untreated and C5a treated) and migrated PMN were incubated for an additional 20 h. At this time point, 69.1% +/- 4.5% and 47% +/- 4.5% of PMN that have migrated through a calfskin-coated membrane and an endothelial monolayer, respectively, were apoptotic, compared with 28.2% +/- 3.0% and 21.1% +/- 4.5% apoptotic untreated and C5a-treated PMN, respectively; 46.9% +/- 4.8% of PMN that have migrated through rat-tail-coated membranes were apoptotic compared with 14.7% +/- 2.3% and 9.3% +/- 1.2% apoptotic untreated and C5a-treated PMN, respectively. Migration across rat-tail collagen-coated membranes with a monolayer of epithelial cells did not affect apoptosis of migrated PMN, even after 20 h of incubation. In conclusion, migration of PMN across collagen-coated membranes (either calfskin or rat-tail collagen) induced an apoptotic response, which was downregulated by a monolayer of endothelial cells and was negated by an epithelial cell monolayer.

Animals↗
PubMed1984

Inhibition of human polymorphonuclear leukocyte cell responses by ibuprofen.

The stimulation of cell swelling, cell aggregation, polymorphonuclear leukocyte locomotion, and lysosomal enzyme release in response to chemoattractant were all inhibited by ibuprofen, a nonsteroidal anti-inflammatory agent. The dosages needed to induce 50% inhibition (ID50) were 5.9, 7.6, 60, and 95 micrograms/mL, respectively. Aside from the differences in ID50, there was also a difference in the degree of maximum inhibition (Imax) of the complement C5a-stimulated responses observed, so that at achievable serum drug concentrations of 20-50 micrograms/mL, inhibition of 67-78% for cell swelling, 69-82% for cell aggregation, 20-35% for migration response, and 17-38% for lysosomal enzyme release were demonstrated. Also observed were a minor stimulatory effect on nitroblue tetrazolium reduction and an inhibitory effect on the ability to kill Staphylococcus aureus, but only at very high concentrations (approximately 2 mg/mL).

Blood Bactericidal Activity↗
PubMed1998

Dialysis neutropenia: the role of the cytoskeleton.

Dialysis neutropenia is the result of pulmonary sequestration of neutrophils after complement activation by the dialyzer membrane. Increased expression of neutrophil adhesion receptors, such as CD11b/CD18, suggests that neutrophil adhesion to the capillary endothelium is a possible mechanism. An alternative hypothesis is that the complement fragment C5a modulates neutrophil mechanical properties via the cytoskeleton-largely filamentous actin (F-actin)-stiffening them and thereby slowing their passage through the pulmonary capillaries. To investigate this hypothesis, we developed an assay to measure the F-actin content of neutrophils in whole blood using flow cytometry and the stain NBD-phallacidin. We measured neutrophil F-actin content during hemodialysis of patients with polysulfone (N = 6), Hemophan (N = 6), and Cuprophan membranes sterilized with either ethylene oxide (N = 5) or steam (N = 6). Cell counts, neutrophil and monocyte CD11b expression and plasma C5a concentrations were also measured. The results confirm the strong relationship between the degree of neutropenia, increases in CD11b expression and plasma C5a levels reported by previous researchers. Modulation of the F-actin content of neutrophils was also strongly related to C5a levels, indicating that the neutrophil cytoskeleton is active during dialysis. Modeling of cell counts suggests that with Cuprophan a substantial fraction of neutrophils and monocytes are sequestered before they even pass through the dialyzer, suggesting some form of systemic activation of these cells. Evidence for systemic activation was also seen in measurements of F-actin content, but not CD11b expression, a finding that strengthens the case for the involvement of the cytoskeleton in dialysis neutropenia.

Actins↗
PubMed1994

Priming for the synthesis of 5-lipoxygenase products in human blood ex vivo by human granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha.

BACKGROUND: Previous studies reported the priming effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF alpha) on leukotriene synthesis by isolated polymorphonuclear leukocytes; however, little is known as of yet of these biologic effects of the two cytokines in a physiologic environment. EXPERIMENTAL DESIGN: In this study, we investigate the effects of GM-CSF and TNF alpha on the synthesis of 5-lipoxygenase (5-LO) products in heparinized blood stimulated ex vivo, using reverse phase high performance liquid chromatography analysis of deproteinized plasma samples. RESULTS: Stimulation of blood with f-Met-Leu-Phe resulted in the accumulation of up to 30 pmol of 5-LO products/ml of plasma. Preincubation of blood with 100 pM GM-CSF or 1.2 nM (200 units/ml) TNF alpha for 30 minutes at 37 degrees C before stimulation with f-Met-Leu-Phe resulted in a marked enhancement (> 5-fold) of the synthesis of leukotriene B4 and 5(S)-hydroxyeicosatetraenoic acid, which were formed in equivalent amounts. GM-CSF and TNF alpha priming activities were detectable at concentrations as low as 3 pM and 6 pM (1 unit/ml), respectively. The preincubation times required for optimal priming by GM-CSF and TNF alpha were different (40 and 10 minutes, respectively), and the effects of the two cytokines on leukotriene B4 and 5(S)-hydroxyeicosatetraenoic acid synthesis were additive, suggesting different priming mechanisms. The synthesis of 5-LO products in primed blood was also induced by platelet-activating factor, the complement fragment C5a, the particulate stimulus zymosan, and the ionophore A23187, but not by interleukin-8. Polymorphonuclear leukocytes and mononuclear cells accounted for 80% and 20% of the synthesis of 5-LO products, respectively. CONCLUSIONS: These data demonstrate that GM-CSF and TNF alpha exert very potent priming effects on the biosynthesis of 5-LO products in whole blood stimulated by various stimuli and strongly support that these cytokines could be important modulators of lipid mediator synthesis in physiologic and pathophysiologic conditions.

Arachidonate 5-Lipoxygenase↗
PubMed2002

The CXC chemokine NAP-2 mediates differential heterologous desensitization of neutrophil effector functions elicited by platelet-activating factor.

During early inflammation, the chemoattractants neutrophil-activating peptide-2 (NAP-2), platelet-activating factor (PAF), and complement component C5a are rapidly generated within the vasculature and potently induce effector functions in neutrophils, such as chemotaxis and degranulation. We investigated whether these mediators would cross-desensitize each other's activities on isolated neutrophils. We demonstrate that NAP-2 and C5a desensitize degranulation of neutrophils in response to PAF. However, whereas C5a-mediated desensitization correlated with the downregulation of PAF binding sites on neutrophils, NAP-2 did not regulate PAF receptors, nor did it modulate their calcium signaling. In further contrast to C5a, which desensitized PAF-induced neutrophil chemotaxis, NAP-2 did not affect the chemotatic response to PAF. These observations indicate that NAP-2 mediates selective desensitization of PAF-induced neutrophil degranulation by a mechanism downstream from PAF receptors, still allowing migration toward PAF. Thus, a role for NAP-2 may be to limit PAF-dependent vascular tissue damage by preventing degranulation of neutrophils without affecting their migration into the inflamed tissue.

Blood Coagulation Factors↗
PubMed2000

Functional heterogeneity of rat hepatic and alveolar macrophages: effects of chronic ethanol administration.

Chronic ethanol consumption is associated with increased incidence of hepatic and pulmonary infections. To determine if this is correlated with altered macrophage activity, we analyzed the functional properties of cells isolated sequentially from the liver and lung of rats fed a liquid diet containing ethanol (35% of calories) or malto-dextrin control for 9-12 weeks. Hepatic and alveolar macrophages from control animals were found to exhibit distinct morphologic and functional properties. Thus, hepatic macrophages were highly vacuolated and appeared larger and more irregular in shape than alveolar macrophages. These cells also displayed greater phagocytic activity and random migration. In contrast, lung macrophages produced more superoxide anion and nitric oxide, and exhibited enhanced chemotactic activity toward the complement fragment C5a. Whereas administration of ethanol to rats for 9-12 weeks resulted in decreased chemotaxis and superoxide anion production by alveolar macrophages, cell adhesion molecule expression was reduced in hepatic macrophages. Nitric oxide production and inducible nitric oxide synthase protein expression were decreased in both macrophage populations. These effects were not observed after 3-6 weeks of ethanol administration to rats. Our results suggest that changes in macrophage functioning may play a role in decreased host defense following chronic ethanol exposure.

Animals↗
PubMed1999

Adenosine A3 receptors on human eosinophils mediate inhibition of degranulation and superoxide anion release.

The role of adenosine A3 receptors on human eosinophil degranulation and superoxide anion (O2-) release was studied in vitro using the complement fragment C5a as the main stimulus and employing a number of selective agonists and antagonists. In the presence of cytochalasin B (CB), C5a induced a dose-dependent release of the granular eosinophil peroxidase (EPO), but not O2-, whereas in the absence of CB O2- , but not EPO, was released. C5a-induced EPO release was inhibited dose-dependently by the selective A3 agonist N6-(3-iodobenzyl)-5'-N-methylcarbamoyladenosine (IB-MECA) and to a lesser extent by the less-selective N6-2-(4-amino-3-iodophenyl) ethyladenosine (APNEA). The IC50 (95% CI) for IB-MECA was 6.8 microM (3.1-12.0 microM). At concentrations up to 100 microM, neither adenosine nor the selective A1 agonist N-cyclopentyladenosine (CPA) and the selective A2 agonist 2-[[2-[4-(2-carboxyethyl)phenyl]ethyl]amino]-N-ethylcarboxamidoadenosine (CGS 21680) had any significant effect. The inhibitory effect of IB-MECA was almost completely abolished by pre-treatment with 1 microM of the selective A3 antagonist 9-chloro-2-(2-furyl)-5-phenylactylamino[1,2,4]triazolo[1,5-c]quina zoline (MRS 1220), but not the selective A1 antagonist 1,3-dipropyly-8-cyclopentylxanthine (DPCPX) or the selective A2 antagonist 3,7-dimethyl-1-propargylxanthine (DMPX). IB-MECA also significantly inhibited C5a-induced O2- release with IC50 (95% CI) of 9.5 microM (4.6-13.1 microM) whereas adenosine and the A1 agonist CPA potentiated this effect at low concentrations. The potentiation appeared to be a result of their direct O2- release from these cells, probably mediated via A1 receptors. The inhibition by IB-MECA was selectively reversed by MRS 1220. These results show that the A3 receptors on human eosinophils mediate inhibition of both degranulation and O2- release and suggest a therapeutic potential for A3 agonists in diseases such as asthma in which activated eosinophils are involved.

Cell Degranulation↗
PubMed1994

Effects of alpha-1 acid glycoprotein on human polymorphonuclear neutrophils: influence of glycan microheterogeneity.

The biological functions of alpha-1 acid glycoprotein (AGP) are poorly understood but appear to depend on glycan microheterogeneity. Variations of AGP glycan structure (in terms of concanavalin A (ConA) reactivity) have been observed during the inflammatory process. We studied these modifications in AGP from patients with chronic renal impairment and investigated the effects of AGP microheterogeneity on healthy polymorphonuclear leukocyte (PMN) chemotaxis and oxidative metabolism. AGP was extracted by a two-step procedure from sera from ten patients with various degrees of renal impairment, selected according to AGP glycan heterogeneity determined by crossed immunoaffinity electrophoresis with ConA. AGP (0.5 g/l) significantly inhibited the chemotactic response of PMN to formyl-methionyl-leucyl-phenylalanine (10(-7) mol/l) and complement fraction C5a, regardless of ConA reactivity. AGP also inhibited superoxide anion generation in response to phorbol myristate acetate (10(-7) mol/l). After stimulation by opsonized zymosan (1 g/l), the effect of AGP appeared to depend on its glycan structure (r = 0.70, P < 0.05), decreasing with ConA non-reactivity. These data suggest that AGP can down-regulate neutrophil responsiveness, an effect that depends in part on its glycan microheterogeneity. Alterations of AGP microheterogeneity in various pathological states, particularly renal failure, may be related to the inflammatory process.

Adult↗
PubMed1993

Upregulation of formyl-peptide and interleukin-8-induced eosinophil chemotaxis in patients with allergic asthma.

BACKGROUND: The cytokine granulocyte-macrophage colony-stimulating factors, interleukin-3 and interleukin-5, are important modulators of eosinophilia and eosinophil function. In particular, eosinophil chemotaxis is very sensitive to cytokine priming. METHODS: We evaluated chemotactic responses of eosinophils from patients with allergic asthma. These cells exhibited a primed phenotype as deduced from enhanced responses toward formyl-methionyl-leucyl-phenylalanine and platelet-activating factor and a decreased responsiveness toward granulocyte-macrophage colony-stimulating factor. Bronchoprovocation of patients with allergic asthma with allergen was performed as a possible means to enhance in vivo priming. RESULTS: Indeed, eosinophils isolated 3 hours after allergen challenge exhibited a more pronounced primed phenotype, which was reflected by an induction of responsiveness towards interleukin-8. Eosinophil responses induced by platelet-activating factor, formyl-methionyl-leucyl-phenylalanine, complement fragment C5a, interleukin-3, interleukin-5, and granulocyte-macrophage colony-stimulating factor were not significantly altered after allergen challenge. CONCLUSION: These data provide further evidence that eosinophils are already primed in the peripheral blood of individuals with allergic asthma. This is most likely due to the presence of circulating cytokines in the peripheral blood of those individuals. This in vivo priming results in selective upregulation and downregulation of responses toward various chemotaxins, which may be released in the lungs during allergic inflammation.

Adult↗
PubMed1982

Defects of serum chemoattraction and polymorphonuclear leucocyte movement in patients with primary hepatocellular carcinoma.

Movement of polymorphonuclear leucocytes to the site of tumour cells may be an important stage in host defences against tumours in a variety of organs. In this study, sera from 29 of 30 patients with primary hepatocellular carcinoma had reduced ability to stimulate the movement in vitro of normal polymorphonuclear leucocytes. The serum defect was more severe in 11 patients with underlying cirrhosis but was not related to abnormalities of tests of liver function, levels of serum alphafetoprotein, or deficiency of complement factors C3 and C5. Serial studies showed that the defect was persistent and progressive in patients in whom the tumour did not respond to treatment. In 35% of patients, mainly those with cirrhosis, the sera contained antagonists to normal serum chemotactic factors which were heat stable and dialysable, but could be distinguished by their effect on complement factor C5a. A heat labile dialysable antagonist(s) was found in sera from 28% of the patients (mainly those without cirrhosis) which antagonized the movement of normal polymorphonuclear leucocytes (cell directed antagonism). In addition to these serum defects, polymorphonuclear leucocytes from two of seven patients studied had reduced movement which was not related to the presence in the serum of cell directed antagonists. These serum and cellular defects have not been reported previously in patients with primary hepatocellular carcinoma, and could compromise the body's defences against the tumour.

Adolescent↗
PubMed1991

Development of fish peritoneal macrophages as a model for higher vertebrates in immunotoxicological studies. I. Characterization of trout macrophage morphological, functional, and biochemical properties.

The immune defense mechanisms of fish are not as well characterized as those of mammals but seem to be related and similarly competent. Because of this, there is an increased interest in the immune responses of fish as models for higher vertebrates in immunotoxicological studies. Prior to such studies, baseline criteria for specific components of the immune response needed to be established. For this study, we have examined trout macrophage morphology using light and scanning electron microscopy, phagocytic activity, random and stimulus-directed migration, and superoxide anion radical (O2-) production for resident and lipopolysacharide (LPS) or Aeromonas salmonicidae-elicited rainbow trout (Oncorhynchus mykiss) peritoneal macrophages (M phi). Following peritoneal lavage, greater than 89% of the cells were M phi as determined by differential counts and nonspecific esterase staining. Immunization with LPS and A. salmonicidae increased M phi number approximately 5 and 13-fold, respectively, and overall size. Trout M phi were phagocytically active engulfing serum opsonized latex particles and were mobile, migrating both randomly and in a directed fashion towards formyl-methionine-L-leucine-L-phenylalanine (FMLP) and trout serum-derived complement fragment C5a. Concentrations of FMLP (100 nM) and C5a (0.01-1%) effective for attracting trout M phi are the same as those used to attract rabbit M phi. Resident trout M phi produced negligable quantities of .O2- following stimulation with 1 micrograms/ml phorbol myristate acetate; Aeromonas-elicited M phi produced .O2- in a time-dependent manner which peaked after 60 min at 2.9 nmol per 2 x 10(5) cells and then declined. The results of this study provide a data base for future toxicological studies with trout peritoneal M phi and indicate the usefulness of this system for immunotoxicological studies.

Aeromonas↗
PubMed1997

Clinical characterization of Dicea a new cellulose membrane for haemodialysis.

A prospective randomised clinical study comparing the functional performance and biocompatibility of a new cellulose diacetate variant (Dicea) in which the degree of hydroxyl group substitution differs, with cellulose diacetate and low flux polysulfone incorporated into commercially produced hollow fiber hemodialysers with a surface area 1.5-1.6 m2 has been undertaken. All dialysers studied demonstrated clinically acceptable performance in terms of their small molecular removal characteristics, with minor statistical but not clinical differences. Use of both cellulose diacetate membranes but not low flux polysulfone resulted in a reduction in plasma beta(2) microglobulin levels. The membranes were impermeable to albumin, but showed some permeability to low molecular weight proteins. The average protein recovery from the dialysis fluid was 3105 mg for Dicea, 2913 mg for cellulose diacetate and 2842 mg for low flux polysulfone. For Dicea the white cell count by 15 minutes had declined to 68% of pre treatment value, compared with 59% and 86% for cellulose diacetate and low flux polysulfone. The differences between Dicea and cellulose diacetate were not significant, but both cellulose based membranes differed from low flux polysulfone (p = 0.0015). There was a strong evidence of differences between the membranes in respect of C5a and C5b-9 generation (p = 0.0001) but not for C3a (p = 0.16) furthermore the levels of C5b-9 generated during dialysis also showed a significant positive correlation compared to C5a for all membranes. (Pearson's correlation coefficient = 0.856, p = 0.0001). It is concluded that the two cellulose diacetate membranes are not identical, with the differences observed being a consequence of the degree of acetyl substitution, resulting in alteration of membrane structure and the method of sterilization. The clinical significance of these differences are difficult to characterize but the modification of the cellulose structure appears to be a promising method to improve the biocompatibility of cellulose membranes. The improved biocompatibility offered by this method still falls short of that achieved with low flux synthetic membranes such as Fresenius Polysulfone.

Adult↗
PubMed1997

Circulating promyelocytes and low levels of CD16 expression on polymorphonuclear leukocytes accompany early-onset periodontitis.

Early-onset periodontitis (EOP) is characterized by rapidly progressive alveolar bone loss, chemotactic defects of neutrophils, and significant familial aggregation. We found immature myeloid lineage cells, defined as promyelocytes, in the peripheral blood in patients with EOP. A hematological examination of peripheral blood cells showed normal reference values regarding cell proportions. Flow cytometry revealed significantly lower expression of CD16, a glycosylphosphatidylinositol (GPI)-anchored protein, on peripheral neutrophils in patients compared with those in age- and sex-matched healthy controls, whereas the levels of CD11a and CD11b expression were similar. The chemotactic response of neutrophils was lower toward not only formyl-methionyl-leucyl-phenylalanine but also complement fragment C5a than that of healthy controls. The expression of another GPI-anchored protein, CD14, was equally expressed by controls and patients. Therefore, the low level of CD16 expression was not due to the incomplete synthesis of the GPI anchor. GPI anchors of CD16 on neutrophils from controls and patients were both partially resistant to phosphatidylinositol-specific phospholipase C. The presence of promyelocytes in peripheral blood, low expression of CD16, and low chemotactic response of neutrophils suggest that patients with EOP have an abnormal maturation system in myeloid lineage cells in the bone marrow, which may be associated with the onset and course of EOP.

Adult↗
PubMed1984

Inhibition of human neutrophil secondary granule discharge by antiinflammatory agents.

Human neutrophil cobalamin binding protein (NCBP) is located exclusively in the neutrophil secondary granules. The soluble stimuli formlymethionyl-leucyl-phenylalanine and the low-molecular-weight complement fragment C5a both promote the dose-dependent release of NCBP from cytochalasin B-treated neutrophils in vitro. The extracellular discharge of NCBP induced by higher secretagogue is inhibited by prior exposure of neutrophils to the corticosteroids hydrocortisone and methylprednisolone and the nonsteroidal antiinflammatory agents indomethacin and ibuprofen. The four antiinflammatory agents function as competitive antagonists of neutrophil secondary granule discharge with a site of action at or near the cell surface. These findings support the hypothesis that antiinflammatory agents prevent neutrophil activation in vitro by inhibition of stimulus-receptor coupling. The significance of these observations with regard to the in vivo actions of these agents remains uncertain, however.

Anti-Inflammatory Agents↗