Neutrophil CD11b,L-selectin and Fc IgA receptors in patients with dermatitis herpetiformis

BACKGROUND: The skin lesions found in patients with dermatitis herpetiformis (DH) are characterized by the presence of neutrophils at the dermal papillary tips in areas where the diagnostic cutaneous IgA deposits are found. Although the presence of the skin lesions of DH is known to be associated with gluten-sensitive enteropathy, the mechanisms that control the development of skin lesions are not known. OBJECTIVES: To determine if circulating neutrophils from patients with DH have evidence of priming as shown by increased expression of CD11b, decreased expression of L-selectin and increased function of neutrophil Fc IgA receptor. METHODS: Neutrophils from 12 normal subjects and 10 DH patients with active, ongoing disease and 14 DH patients with quiescent disease activity were examined by fluorescence-activated cell sorter for expression of cell surface CD11b, L-selectin expression, Fc IgA expression (CD89) and for the function of the Fc IgA receptor by determining the binding capacity of neutrophils for monoclonal human IgA. RESULTS: Neutrophils from patients with active, ongoing DH had increased expression of CD11b when compared with patients with inactive DH or normal subjects [mean net geometric mean channel fluorescence (GMCF): active DH, 403.3; inactive DH, 237.8; normal subjects, 290.5; P < 0.05]. L-selectin expression in both groups of DH patients was significantly lower than that seen in normal subjects (mean net GMCF: active DH, 363.2; inactive DH, 375.2; normal subjects, 432.7; P < 0.05). No difference in CD89 expression was seen in any of the groups; however, the function of Fc IgA receptor was increased in patients with active DH when compared with patients with inactive DH and normal subjects. CONCLUSIONS: Neutrophils from patients with active, ongoing DH show an increased expression of CD11b, decreased expression of L-selectin and increased ability to bind IgA, consistent with a pattern of priming of the neutrophils. This priming may occur in the gut as a result of the ongoing mucosal immune response that is present in patients with DH on a gluten-containing diet and may predispose neutrophils to localize in the skin of patients with DH.     

Effects of different preparations of propofol, diazepam, and etomidate on human neutrophils in vitro

BACKGROUND: Intravenous anaesthetics and sedatives can influence polymorphonuclear cell (PMN) functions. Some of the drugs for sedation and anaesthesia have been alternatively dissolved in lipid solutions containing medium (MCT) and/or long chain (LCT) triglycerides. The in vitro effects of two different diazepam (benzyl-alcohol, LCT/MCT), etomidate (propylene-glycol, LCT/MCT), and propofol (LCT, LCT/MCT) preparations on respiratory burst (RB) and phagocytosis of human PMNs were studied. METHODS: Diazepam (2, 20 microg ml(-1)), etomidate (0.5, 5 microg ml(-1)), and propofol (6, 60 microg ml(-1)) were investigated in clinical and 10-fold concentrations with flow cytometric assays. The RB was measured with the fluorescent dye rhodamine after induction with Escherichia coli or formyl-methionyl-leucylphenylalanine (FMLP) following priming with tumour necrosis factor alpha (TNF-alpha). Phagocytosis of PMNs was carried out in whole blood after incubation with fluorescein-labelled E. coli. RESULTS: LCT-propofol at 60 microg ml(-1) reduced the percentage of PMNs with RB activity after induction with E. coli (52.8+/-20.4) and TNF-alpha/FMLP (10.8+/-5.1)) as well as the percentage of phagocytosing PMNs (48.9+/-19.5) in contrast to LCT/MCT-propofol, which augmented all parameters (85.4+/-10.1, 50.3+/-12.7, 66.5+/-12.5). Also the higher concentrations of LCT/MCT-diluted etomidate and diazepam increased the percentage of RB positive PMNs compared to the alternative compositions. The percentage of phagocytosing PMNs was less reduced with 20 microg ml(-1) LCT/MCT-diazepam (85.2+/-6.9) than with the same concentration of benzyl-alcohol diluted diazepam (68.8+/-12.2) compared to the control. CONCLUSION: The in vitro effects of diazepam, etomidate, and propofol are dependent on the solvent applied. The tested LCT/MCT preparations reduce the inhibitory effects on the bacterial killing capacity of PMNs found after incubation with propyleneglycol, benzyl-alcohol, or LCT preparations, respectively.     

Nasal inflammation and chronic ear disease in Australian Aboriginal children

Objective : Chronic middle ear disease is common in Aboriginal children, and may be linked to nasal inflammation and Eustachian tube dysfunction. The pattern of nasal inflammation is unknown. The study reported here was performed to define the role of allergy and infection in causing nasal inflammation in Aboriginal children with chronic middle ear disease.
Methodology : Thirty-one Aboriginal children aged between 3 and 7 years underwent clinical assessment, audiometry and allergy skin tests. Nasal swabs for bacterial culture and cytology were performed during the winter and again in spring to identify any seasonal variation. A randomized trial of nasal beclomethasone for 8 weeks was conducted in children with abnormal tympanometry to identify the effect of therapy upon nasal cytology.
Results : Twenty-six of the 31 children had abnormal tympanograms. Average hearing levels were reduced in nine children. Pathogenic organisms were isolated from most children: Streptococcus pneumoniae (82%), Haemophilus influenzae (79%), Moraxella catarrhalis (39%) and Staphylococcus aureus (29%). Eight of the 31 children (26%) were atopic. Nasal cytology disclosed a marked neutrophil infiltrate (80% of cells) during the winter, which fell significantly in spring to 52% of cells. Only two subjects had nasal eosinophilia of >10%. There was no effect of beclomethasone on nasal cytology.
Conclusions : Chronic ear disease in Aboriginal children is associated with nasal inflammation, neutrophil infiltration and the presence of bacteria. These features suggest respiratory infection as the main cause of chronic nasal inflammation in Aboriginal children with middle ear disease. There is a seasonal variation in the severity of the nasal infiltrate, consistent with increased infections during winter. Despite a high prevalence of atopy, allergic nasal disease was uncommon.     

NITROBLUE-TETRAZOLIUM REDUCTION BY NEUTROPHILS OF NEWBORN INFANTS IN IN VITRO PHAGOCYTOSIS TEST

Venous blood from healthy premature infants, premature infants with known bacterial infections, normal term infants and adults, was incubated in vitro with Pseudomonas aeruginosa. At 30 min intervals, blood samples were tested for the nitroblue-tetrazolium (NBT) reducing activity of neutrophils. The results of the histochemical NBT test were compared with those of the blood controls from which bacteria were omitted. The stimulation of neutrophils with Ps. aeruginosa induces a considerable increase of NBT reduction in all 4 groups of subjects examined. The maximum rate of NBT reduction was observed after 1 hour of incubation with the test organism, and reached its lowest degree after 3 hours. By contrast the NBT reduction by un-stimulated neutrophils of the same subjects remain unchanged during a 3 hour period of incubation.     

Neutrophil and macrophage activation and anaphylatoxin formation in orthotopic liver transplantation without the use of veno-venous bypass

Background. Activation of neutrophils and activation of complement may be an aetiologic factor behind circulatory insufficiency in association with reperfusion of the grafted liver.
Methods. Neutrophil and macrophage activation (determined as PMN elastase and neopterin release) and complement activation were evaluated in 15 consecutive patients undergoing orthotopic liver transplantation without the use of veno-venous bypass.
Results. The PMN elastase concentrations were increased at the end ot the anhepatic phase, 2, 5 and 30 min after start of reperfusion and 6 and 24 h postoperatively. There were significantly higher PMN elastase concentrations in patients with circulatory instability (postreperfusion syndrome) compared with those without postreperfusion syndrome. The neopterin concentration was increased 2 min after the start of reperfusion and remained elevated until 6 h postoperatively. The plasma complement C3a concentrations were increased at the end of the anhepatic phase and 2, 5 and 30 min after the start of reperfusion. The plasma C3a levels were higher in patients with postreperfusion syndrome compared to those without.
Conclusions. Activation of neutrophils and macrophages and of the complement cascade with the formation of biologically active substances may be one explanation for the circulatory instability often seen in patients undergoing orthotopic liver transplantation.     

The influence of plasma proteins on the distribution of leucocytes within the brain parenchyma in a murine model of stroke

Inflammatory responses are thought to play an important role in the exacerbation of neuronal loss following stroke. Leucocyte recruitment following cerebral ischaemia has been demonstrated in experimental animals, and procedures which reduce the entry of leucocytes into the brain reduce neuronal loss and improve aspects of functional recovery in these models. In this study we investigate whether leakage of plasma proteins into the central nervous system (CNS) following ischaemia influences leucocyte adhesion within the parenchyma. Using an in vitro adhesion assay, we demonstrate that the addition of exogenous serum proteins increases macrophage adhesion to CNS tissue. Following permanent middle cerebral artery occlusion (MCAO) in mice, plasma proteins leak into the apparently healthy cortex surrounding the infarcted area. We show that there is increased macrophage adhesion to sections in the border region where endogenous plasma proteins are present within the parenchyma. Using immunohistochemistry, we co-localize plasma protein distribution within the tissue with leucocyte recruitment following MCAO. We show that monocytes, not neutrophils, infiltrate the lesion border where plasma proteins are present in the parenchyma. This distribution is compatible with their contributing to neuropathology, whereas neutrophils are found in clusters in the lesion core. We conclude that leakage of plasma proteins into the brain could influence leucocyte adhesion within the parenchyma. Recruited monocytes may exacerbate neuropathology in situations such as permanent cerebral ischaemia, where disruption of the blood–brain barrier occurs.     

PERITONEAL NEUTROPHILIA: A POTENTIAL INDICATOR OF THE SURGICAL ACUTE ABDOMEN

The percentage of neutrophils in a peritoneal cell sample (PNP), obtained at operation, was measured in 250 patients who underwent urgent laparotomy because ‘the surgical acute abdomen’ (SAA) was suspected. The PNP was substantially higher in patients with confirmed SAA than in others and is potentially a very sensitive and very specific test of SAA. If the PNP was available as a diagnostic test for patients with acute abdominal pain, there might be a significant reduction in unnecessary and delayed laparotomies.     

Effect of Ulinastatin, a human urinary trypsin inhibitor, on the oleic acid-induced acute lung injury in rats via the inhibition of activated leukocytes

BACKGROUND: The acute respiratory distress syndrome (ARDS) is often caused by fat tissue embolism. One of the most common animal models of ARDS is produced by direct administration of oleic acid (OA). Activated leukocytes are critically involved in the pathological mechanism in this model. Human urinary trypsin inhibitor (UTI) is known to inhibit production of tumor necrosis factor (TNF)-alpha, which potently stimulates leukocyte activation. The purpose of this study was to clarify whether UTI improves OA-induced lung injury in rats by inhibiting activated leukocytes via TNF-alpha production. MATERIALS AND METHODS: Rats were subjected to a single intravenous administration of OA into the pedicle vein. Acute lung injury was evaluated by arterial blood gases and histological changes in lungs. Pulmonary vascular permeability, accumulation of neutrophils, and the levels of TNF-alpha in lung tissues were also examined. Rats were divided into four experimental groups: a sham operated, OA, OA + UTI, and OA + nitrogen mustard (NM)-induced leukocytopenia group. UTI was intravenously administered 30 min before OA administration. Leukocytopenia was induced by the administration of NM. RESULTS: UTI significantly improved the OA-induced histological changes for 4 h after OA administration. The OA-induced reduction of PaO2, the increase of pulmonary vascular permeability, and the levels of MPO activity and TNF-alpha in lung tissues were significantly improved in rats administrated UTI. The effects in the leukocytopenia group were similar to those in the UTI-administered group. CONCLUSION: Leukocytes play a critical role in the development of OA-induced lung injury. It was suggested that UTI contributed to the reduction in the OA-induced lung injury by inhibiting TNF-alpha and thereby suppressing leukocyte.     

ZINC AND POLYMORPHONUCLEAR LEUKOCYTE FUNCTION

Intracellular zinc uptake and concentration is one of the determinants of oxygen consumption, phagocytosis and bactericidal capacity of neutrophils.