Successful treatment of sclerosing cervicitis and fibrosing mediastinitis with tamoxifen.

Fibrosing mediastinitis and sclerosing cervicitis are fibrosclerotic disorders akin to retroperitoneal fibrosis, with presenting symptoms related to local pain or viscus obstruction or both. No definitive treatment is known. This is the first report of these disorders dramatically responding to tamoxifen citrate and prednisone.

Neutrophils are not necessary for ischemia-reperfusion lung injury.

The role of neutrophils (PMNs) in ischemia-reperfusion injury after lung transplantation is unclear. If PMNs are involved in ischemia-reperfusion injury in the intact rat, then PMNs should sequester in the injured lung and PMN-depleted rats should develop less injury. Group A rats were treated with a rabbit anti-rat PMN antibody causing profound neutropenia (less than 100 PMNs/microL) and group B with control serum (greater than 2,000 PMNs/microL). Rats were anesthetized and left lung ischemia was sustained for 90 or 180 minutes by clamping the bronchus and the pulmonary artery and vein. Lung injury was quantified by the accumulation of radiolabeled (125I) albumin in ischemic left and nonischemic right lungs (cpm per gram of lung/cpm per gram of blood). Ischemia caused significant lung injury (p less than 0.05) in both PMN-depleted (albumin leak index: 90 min, 0.208; 180 min, 0.218) and nondepleted (90 min, 0.222; 180 min, 0.241) animals compared with nonischemic controls (depleted: 90 min, 0.050; 180 min, 0.100; nondepleted: 90 min, 0.063; 180 min, 0.101); microscopy also demonstrated lung injury. The injury was not associated with PMN sequestration as shown by light microscopy. Thus, we conclude that PMNs are not necessary for ischemia-reperfusion injury and PMN-depletion does not attenuate ischemia-reperfusion injury.

Inhibition of cyclooxygenase metabolite production attenuates ischemia-reperfusion lung injury.

We investigated if cyclooxygenase metabolites of arachidonic acid were involved in ischemia-reperfusion lung injury by determining if inhibition of their production attenuated the injury. Isolated rat lungs were perfused with physiologic salt solution osmotically stabilized with Ficoll until circulating blood elements were not detected in lung effluent. Ischemia was induced by stopping ventilation and perfusion for 90 min. Lung ventilation and perfusion were then resumed. Ischemia-reperfusion resulted in the production of prostacyclin and thromboxane assessed by lung effluent and tissue measurements of their respective stable metabolites, 6-keto-PGF1 alpha thromboxane B2 (TxB2). In contrast, prostaglandin F2 alpha did not increase. Ischemia-reperfusion also caused lung injury as assessed by increased lung 125I-BSA accumulation compared with nonischemic control lungs. Addition of the cyclooxygenase inhibitors, indomethacin, or flubiprofen to the lung perfusate before and after ischemia inhibited lung injury as well as the production of 6-keto-PGF1 alpha and TxB2. Addition of a thromboxane synthetase inhibitor (U 63557A) reduced lung injury as well as TxB2 formation without affecting the production of 6-keto-PGF1 alpha. The attenuation of lung injury was not explained by direct H2O2 removal by indomethacin, flubiprofen, or U 63557A because the concentrations of the inhibitors used in the isolated lung experiments did not remove exogenously added H2O2 from buffer in vitro. We conclude that cyclooxygenase metabolites of arachidonic acid are involved in ischemia-reperfusion injury to isolated rat lungs.

Iloprost inhibits neutrophil-induced lung injury and neutrophil adherence to endothelial monolayers.

We hypothesized that Iloprost, a long-acting prostacyclin analog, would inhibit neutrophil (PMN)-induced lung injury and decrease PMN adherence to vascular endothelium. Human PMNs infused into isolated buffer-perfused rat lungs subsequently stimulated with phorbol myristate acetate (PMA) resulted in lung injury as assessed by the accumulation of [125I]bovine serum albumin (125I-BSA) in lung parenchyma and alveolar lavage fluid. Addition of Iloprost to the lung perfusate, prior to activation of the PMNs, reduced lung injury as assessed by a decrease in the accumulation of 125I-BSA in the lung. This protective effect was not due to the vasodilatory effect of Iloprost. Protection by Iloprost was not linked to a reduction in PMA-induced PMN superoxide production since Iloprost did not reduce the amount of superoxide released into lung perfusate. In vitro, Iloprost caused a dose-dependent inhibition of PMA-stimulated PMN adherence to endothelial cells. Iloprost did not affect the number of Mo1 adhesion molecules constitutively expressed or the number of receptors expressed on the PMNs following PMA. Addition of cAMP or dibutyryl cAMP to the endothelial cells mimicked the effects of Iloprost, diminishing PMA-stimulated PMN adhesion. In separate experiments, addition of the phosphodiesterase inhibitor IBMX to Iloprost resulted in a greater inhibition of PMA-stimulated PMN adherence, while addition of an adenylate cyclase inhibitor, SQ 22,536, or cAMP antibodies with the Iloprost abolished Iloprost's inhibitory effect on PMN adhesion. Thus, Iloprost inhibits PMA-activated PMN-induced lung injury despite continued superoxide production. Iloprost inhibition of PMN adhesion is dependent on cAMP.

Immediate drainage is not required for all patients with complicated parapneumonic effusions.

We retrospectively investigated if the clinical course of complicated parapneumonic effusions was altered by treatment with immediate drainage plus antibiotics vs antibiotics alone. The two groups of patients had no significant differences in age, duration of symptoms prior to hospitalization, initial maximum temperature, WBC count, or characteristics of the pleural fluid. There were no differences in the duration of hospitalization, fever, elevated WBC count, intravenous antibiotic therapy, or the time for roentgenographic resolution of the effusions. There was one death in each group. The infection of the pleural space resolved in 13 of 16 patients treated with antibiotics alone. No recurrence of the infection of the pleural space occurred in these patients. Antibiotics alone were not sufficient in two cases which eventually required chest tube drainage. Therefore, not all complicated parapneumonic effusions require drainage. A prospective study is required to determine if chest tube drainage should be part of the initial management of complicated parapneumonic effusions.

C3a57-77, a C-terminal peptide, causes thromboxane-dependent pulmonary vascular constriction in isolated perfused rat lungs.

Pulmonary hypertension occurs after the intravascular activation of complement. However, it is unclear which activated complement fragments are responsible for the pulmonary vascular constriction. We investigated the 21-carboxy-terminal peptide of C3a (C3a57-77) to see if it would cause pulmonary vascular constriction when infused into isolated buffer-perfused rat lungs. Injection of C3a57-77 (225 to 450 micrograms) caused mean pulmonary arterial pressure (Ppa) to rapidly increase. However, the response was transient, with Ppa returning to baseline within 10 min of its administration. C3a57-77 also resulted in an increase in lung effluent thromboxane B2 (TXB2), concomitant with the peak increase in Ppa. C3a57-77 did not affect the amount of 6-keto-PGF1 alpha in the same effluent samples. Indomethacin inhibited the C3a57-77-induced pulmonary artery pressor response and the associated TXB2 production. Indomethacin also decreased lung effluent 6-keto-PGF1 alpha. The thromboxane synthetase inhibitors CGS 13080 and U63,357 inhibited the C3a57-77-induced pulmonary artery pressor response and TXB2 production without affecting 6-keto-PGF1 alpha. These inhibitors did not inhibit pulmonary artery pressor responses to angiotensin II. Tachyphylaxis to C3a57-77 occurred because a second dose of C3a57-77 administered to the same lung failed to cause a pulmonary artery pressor response or TXB2 production. The loss of the pressor response was not due to a C3a57-77-induced decrease in pulmonary vascular responsiveness because pressor responses elicited by angiotensin II were not altered by lung contact with C3a57-77. Thus, C3a57-77 caused thromboxane-dependent pulmonary vascular constriction in isolated buffer perfused rat lungs.

Neutrophils are not necessary for induction of ischemia-reperfusion lung injury.

Ischemia-reperfusion lung injury limits lung transplantation. Neutrophil activation and/or xanthine oxidase-mediated purine degradation may cause toxic oxygen metabolite production and lung injury. We investigated whether circulating blood elements are involved in the pathogenesis of ischemia-reperfusion lung injury. Isolated rat lungs were perfused with physiological salt solution (PSS) stabilized with Ficoll until circulating blood elements were not detected in the lung effluent. Lungs were then rendered ischemic by stopping ventilation and perfusion for 45 min at room temperature. Lung injury occurred and was quantitated by the accumulation of 125I-bovine serum albumin into lung parenchyma and alveolar lavage fluid during reperfusion. Lung injury occurred, in the absence of circulating blood elements, when ischemic lungs were reperfused with PSS-Ficoll solution alone. Reperfusion with whole blood or PSS-Ficoll supplemented with human or rat neutrophils did not increase lung injury. Furthermore, during lung ischemia, the presence of neutrophils did not enhance injury. Experiments using PSS-albumin perfusate and quantitating lung injury by permeability-surface area product yielded similar results. Microvascular pressures were not different and could not account for the results. Toxic O2 metabolites were involved in the injury because addition of erythrocytes or catalase to the perfusate attenuated the injury. Thus reperfusion after lung ischemia causes injury that is dependent on a nonneutrophil source of toxic O2 metabolites.

Inhibition of rat lung glutathione synthesis attenuates hypoxic pulmonary vasoconstriction and the associated leukotriene C4 production.

Lipoxygenase metabolites of arachidonic acid have been proposed as possible mediators of hypoxic pulmonary vasoconstriction (HPV) in the rat. Since reduced glutathione (GSH) is a required substrate for the synthesis of the sulfidopeptide eicosanoid leukotriene C4 (LTC4), we reasoned that this specific GSH dependence of LTC4 synthesis might allow us to distinguish between the roles of sulfidopeptide leukotrienes and other 5-lipoxygenase metabolites of arachidonic acid. In the present study we have examined the effect of in vivo pretreatment with the GSH synthesis inhibitor buthionine sulfoximine (BSO) on both the hypoxic pressor response and lung leukotriene synthesis in the rat. The intraperitoneal administration of 4 mmol/kg of BSO 30, 20, and 4 h prior to lung excision significantly depleted total lung glutathione as compared to saline-pretreated controls. This depletion of glutathione was associated with a significant attenuation of HPV in isolated perfused lungs but no alteration in pressor response to angiotensin II or KCl. In addition, hypoxia-associated LTC4 levels in lung homogenates were significantly lower in animals pretreated with BSO than in saline-pretreated controls. The specificity of the effects of BSO on lung leukotriene synthesis was examined by quantitating immunoreactive leukotrienes produced by unstimulated and ionophore A23187-stimulated parenchymal lung fragments, lonophore stimulation of lung fragments from BSO-pretreated rats produced 76 +/- 12.2% as much LTC4 and 127 +/- 22.3% as much leukotriene B4 as did fragments from saline-pretreated rats. Our data demonstrating that GSH depletion caused parallel reductions in both HPV and hypoxia-associated lung LTC4 levels are therefore consistent with the hypothesis that sulfidopeptide leukotrienes are involved in this pressor response in the rat.

Surface Mo1 (CD11b/CD18) glycoprotein is up-modulated by neutrophils recruited to sites of inflammation in vivo.

Inasmuch as the recruitment of polymorphonuclear leukocytes (PMNs) to inflammatory foci in vivo involves adhesion-dependent events (e.g., margination, diapedesis, and directed migration), we sought to characterize the relationship between the local accumulation of PMNs in sterile peritonitis and their surface expression of the adhesion-promoting plasma membrane glycoprotein, Mo1 (CD11b/CD18). In an immunofluorescence analysis of PMNs isolated from rats injected intraperitoneally with sterile 1% glycogen solution, we detected a significant enhancement of surface Mo1 expression by exudative peritoneal PMNs. In contrast, no significant rise in Mo1 expression was noted over time by circulating intravascular PMNs (isolated simultaneously). However, these intravascular PMNs had the capacity to increase their surface Mo1 density upon exposure to peritoneal fluid supernatant at 37 degrees C. These results demonstrate that PMNs at sites of inflammation in vivo do up-modulate their surface expression of the adhesion-promoting Mo1 glycoprotein during their recruitment from the circulating, intravascular leukocyte pool.

Lung injury caused by cobra venom factor is reduced in rats raised on an essential fatty acid-deficient diet.

Arachidonate metabolites appear to be involved in lung injury caused by cobra venom factor (CVF)-induced complement and polymorphonuclear leukocyte (PMN) activation. These studies were designed to assess the effects of a dietary-induced deficiency of arachidonic acid on CVF-induced lung injury. Rats raised on an essential fatty acid-deficient (EFAD) diet exhibited the expected changes in fatty acid composition including decreased plasma levels of arachidonic acid and increased levels of 5,8,11-eicosatrienoic acid. In intact rats raised on the EFAD diet, CVF-induced lung injury was attenuated. When blood and excised lungs from rats raised on the normal diet were used, CVF caused pulmonary vascular constriction and acute lung injury, as evidenced by increased 125I-labeled bovine serum albumin accumulation in lung parenchyma and alveolar lavage fluid. The CVF-induced pulmonary artery pressor response and lung injury were reduced when blood perfusate or blood perfusate and excised lungs were obtained from rats raised on the EFAD diet. The pulmonary vascular constriction and lung injury were not attenuated when the blood perfusate was obtained from rats raised on the normal diet, irrespective of whether the excised lungs were obtained from rats raised on the normal or EFAD diet. PMNs obtained from rats raised on the EFAD diet demonstrated decreased superoxide production as well as impaired random migration and chemotaxis in vitro. In contrast, beta-glucuronidase release was quantitatively similar to PMNs from control rats. These data indicate that the EFAD diet-induced attenuation of CVF-induced pulmonary hypertension and acute lung injury is due to defective effector cells in blood rather than modified pulmonary target tissue.

Hypothermia or continuous ventilation decreases ischemia-reperfusion injury in an ex vivo rat lung model.

The susceptibility of lung tissue to ischemia-reperfusion injury has made distant procurement of heart-lung allografts difficult. The effects of hypothermia, ventilation without perfusion, and various reperfusion solutions (PSS/Ficoll or whole blood) on the development of ischemia-reperfusion lung injury were investigated. Use of an ex vivo rat lung model in which the above variables were individually varied permitted a direct approach for these studies. Normothermic ischemia for 1 hour caused significant damage, documented by increased iodine 125 bovine serum albumin (125I-BSA) in alveolar lavage fluid and lung parenchyma compared with nonischemic controls. Hypothermic (4 degrees C) ischemia for 4 hours in lungs reperfused with salt solution and for as many as 12 hours in lungs reperfused with whole blood caused no significant increase in 125I-BSA in alveolar lavage fluid and lung parenchyma compared with nonischemic controls. Lungs ventilated without perfusion showed no increase in 125I-BSA leakage compared with controls. The ex vivo rat lung model is excellent for studying ischemia-reperfusion injury. It is reproducible, allows for variance of reperfusion solutions, and permits change in temperature and ventilation easily.

Cytoplasts and Mo1-deficient neutrophils pretreated with plasma and LPS induce lung injury.

We hypothesized that neutrophil adhesion and lung injury could occur independent of the surface receptor glycoprotein, Mo1 (C3bi receptor). We investigated whether preincubation of human neutrophil-derived cytoplasts (cell fragments that lack nuclei and granules and have a fixed number of surface Mo1 receptors) with plasma and lipopolysaccharide (LPS) would augment the cytoplasts' ability to cause lung injury when activated. We also investigated whether preincubating normal human neutrophils treated with anti-Mo1 antibody with plasma and LPS would increase the neutrophils' ability to adhere and cause lung injury. Human neutrophils infused into isolated salt-perfused rat lungs subsequently stimulated with phorbol 12-myristate 13-acetate (PMA) resulted in lung injury as assessed by the accumulation of 125I-bovine serum albumin in the lung parenchyma. The infusion of cytoplasts resulted in significantly less injury. Cytoplasts preincubated in 20% human plasma and LPS caused an increase in lung injury. Similarly, neutrophils treated with plasma, LPS, and anti-Mo1 antibody or neutrophils congenitally deficient in the Mo1 surface receptor and treated with plasma and LPS augmented lung injury. Plasma and LPS preincubation also increased anti-Mo1 antibody-treated neutrophil adhesion to endothelial cell monolayers after activation by PMA. Thus, plasma and LPS increase adhesion and lung injury caused by neutrophils or neutrophil fragments that share defects in Mo1 receptor expression.

Pancreatitis-induced acute lung injury. An ARDS model.

Cerulein-induced acute pancreatitis in rats is associated with acute lung injury characterized by increased pulmonary microvascular permeability, increased wet lung weights, and histologic features of alveolar capillary endothelial cell and pulmonary parenchymal injury. The alveolar capillary permeability index is increased 1.8-fold after a 3-hour injury (0.30 to 0.54, p less than 0.05). Gravimetric analysis shows a similar 1.5-fold increase in wet lung weights at 3 hours (0.35% vs. 0.51% of total body weight, p less than 0.05). Histologic features assessed by quantitative morphometric analysis include significant intra-alveolar hemorrhage (0.57 +/- 0.08 vs. 0.12 +/- 0.02 RBC/alveolus at 6 hours, p less than 0.001); endothelial cell disruption (28.11% vs. 4.3%, p less than 0.001); and marked, early neutrophil infiltration (7.45 +/- 0.53 vs. 0.83 +/- 0.18 PMN/hpf at 3 hours, p less than 0.001). The cerulein peptide itself, a cholecystokinin (CCK) analog, is naturally occurring and is not toxic and in several in vitro settings including exposure to pulmonary artery endothelial cells, Type II epithelial cells, and an ex vivo perfused lung preparation. The occurrence of this ARDS-like acute lung injury with acute pancreatitis provides an excellent experimental model to investigate mechanisms and mediators involved in the pathogenesis of ARDS.

Xanthine oxidase inhibition attenuates ischemic-reperfusion lung injury.

Ischemic-reperfusion lung injury is a factor potentially limiting the usefulness of distant organ procurement for heart-lung transplantation. Toxic oxygen metabolites are considered a major etiologic factor in reperfusion injury. Although oxygen-free radicals may be generated by many mechanisms, we investigated the role of xanthine oxidase in this injury process by using lodoxamide, a xanthine oxidase inhibitor, to inhibit ischemic-reperfusion injury in an isolated rat lung model. Isolated rat lungs were perfused with physiologic salt solution (PSS) osmotically stabilized with Ficoll until circulating blood elements were nondetectable in the pulmonary venous effluent. Lungs were rendered ischemic by interrupting ventilation and perfusion for 2 hr at 37 degrees C. After the ischemic interval, the lungs were reperfused with whole blood and lung injury was determined by measuring the accumulation of 125I-bovine serum albumin in lung parenchyma and alveolar lavage fluid as well as by gravimetric measurements. Lung effluent was collected immediately pre- and postischemia for analysis of uric acid by high-pressure liquid chromatography. Lodoxamide (1 mM) caused significant attenuation of postischemic lung injury. Uric acid levels in the lung effluent confirmed inhibition of xanthine oxidase. Protection from injury was not complete, however, implying that additional mechanisms may contribute to ischemic-reperfusion injury in the lung.

Discontinuation of mechanical ventilation.

The vast majority of patients who undergo mechanical ventilation are able to discontinue ventilatory assistance within a few days. Typically, patients who require only short-term mechanical ventilation do not have severe underlying lung disease, and the problem for which they require ventilatory support is most commonly rapidly reversible. In these patients on short-term ventilatory support, parameters of spontaneous ventilatory requirements and respiratory muscle strength, including minute ventilation, maximal voluntary ventilation, vital capacity, and maximal inspiratory pressure, are useful in predicting the success of discontinuation of mechanical ventilation. Ventilatory support can generally be discontinued by a variety of techniques in these patients without the need for weaning from the ventilator per se. The smaller group of patients in whom it is not possible to discontinue mechanical ventilation within less than 7 days comprises individuals who frequently have severe acute or chronic lung disease, multisystem extrapulmonary disease, or neuromuscular disease. After a period of prolonged mechanical ventilatory support, these complicated patients require a process of progressive weaning in which they gradually become able to support spontaneous ventilation. Spontaneous ventilatory parameters do not correlate well with weaning ability in patients on long-term ventilatory support. A systematic and comprehensive approach in which attention is focused on optimizing pulmonary and nonpulmonary factors that affect the weaning process provides the best chance for successful withdrawal of ventilatory support after long-term mechanical ventilation. Inadequate ventilatory drive, respiratory muscle weakness and fatigue, increased work of breathing, excessive CO2 production, and cardiac failure are potential mechanisms that may play a role in inhibiting successful weaning. Adverse factors relevant to each of these mechanisms must be addressed and corrected to whatever extent possible. Studies have not demonstrated the superiority of either classic T-piece weaning or IMV weaning methods in difficult-to-wean patients on long-term ventilatory support. Both techniques may be used successfully as long as all patient variables that may adversely affect weaning ability are corrected or optimized and close care and attention to the details of the weaning process itself are provided.(ABSTRACT TRUNCATED AT 400 WORDS)

Eicosanoids are involved in the permeability changes but not the pulmonary hypertension after systemic activation of complement.

Intravenous injection of the complement activator, cobra venom factor (CVF), produces acute lung injury that is neutrophil-dependent and oxygen radical mediated. Using the ex vivo model of lung perfusion, the current studies were designed to measure the appearance of eicosanoids in relation to the development of pulmonary arterial hypertension and vascular permeability. Inhibitors of the cyclooxygenase and lipoxygenase pathways were also employed to assess the possible role of eicosanoids in these two functional responses. Ten minutes after infusion of CVF, when the pulmonary hypertensive changes were maximal, no increases in eicosanoids could be detected in whole lung lavage fluid (TXB2, 6-keto-PGF1 alpha, LTB4, LTC4) or plasma (TXB2, 6-keto-PGF1 alpha) and the inhibitors failed to affect the pressor response. In contrast, lung injury as defined by increased vascular permeability was temporally associated with the appearance in whole lung lavage fluid of TXB2, LTB4 and LTC4, the presence of which was blocked by the relevant inhibitors. Lung injury was attenuated by both cyclooxygenase and lipoxygenase inhibitors. This effect was not peculiar to the isolated lung model since cyclooxygenase (ibuprofen, indomethacin) and lipoxygenase (nafazatrom, U66,855) inhibitors also attenuated the CVF-induced increased vascular permeability in intact rats. These data suggest that in the model system employed eicosanoid production is linked to increases in lung vascular permeability but not to pulmonary artery hypertension.

Modulation of surface CD11/CD18 glycoproteins (Mo1, LFA-1, p150,95) by human mononuclear phagocytes.

Mo1, LFA-1, and p150,95 are structurally related glycoproteins of the CD11/CD18 complex that are expressed on the membrane of human leukocytes. In the neutrophil, the surface expression of the CD11/CD18 complex is up-modulated (Mo1 greater than p150,95 much greater than LFA-1) by stimulatory factors that include calcium ionophore A23187, phorbol myristate acetate (PMA), and N-L-formyl-L-leucyl-L-phenylalanine (fMLP). Here, in an immunofluorescence analysis, we have examined CD11/CD18 glycoprotein expression by human monocytes, pulmonary alveolar macrophages (PAM, obtained by bronchoalveolar lavage), and breast milk macrophages (BMM) as compared to neutrophils before and after exposure to A23187 (1 microM), fMLP (0.1 microM), or PMA (0.1 microgram/ml) for 15 min at 37 degrees C. Unstimulated monocytes within unfractionated blood mononuclear cells kept at 4 degrees C (n = 13) expressed all three CD11/CD18 glycoproteins, and exposure to A23187 resulted in significant increases in the surface expression of Mo1 (median of 5.7-fold), LFA-1 (median of 2.1-fold), and p150,95 (median of 7.2-fold). Exposure to fMLP- or PMA-stimulated increases of lesser magnitude. CD11/CD18 expression by PAM (n = 9) was barely detectable and was unaffected by exposure to A23187. In contrast, BMM (n = 11) expressed all three CD11/CD18 glycoproteins (with considerable variability among specimens), but no increase was stimulated by A23187. These results demonstrate that monocytes, like neutrophils, have the capacity to respond to activating factors with an increase in CD11/CD18 glycoprotein expression; macrophage differentiation is accompanied by a loss (PAM) or retention (BMM) of CD11/CD18 expression that is unmodulated in response to activation.

Neutrophil function disorders.

The polymorphonuclear leukocyte (neutrophil) is the most important phagocytic cell that defends the host against acute bacterial infection. Disorders of neutrophil function are suggested by recurrent cutaneous, periodontal, respiratory, or soft tissue infections. Staphylococcus aureus, gram-negative bacilli, and less commonly, Candida albicans, are the causative organisms. Treatment is supportive involving surgical drainage and antibiotics. Bone marrow transplantation offers hope to some patients. The biochemical and molecular defects have been identified for some of these disorders. Identification of these defects and their physiologic consequences have improved our understanding of how the activated neutrophil is attracted and adheres to inflammatory sites, and produces toxic products that destroy bacteria. However, the activated neutrophil may also damage normal tissue and participate in diseases such as rheumatoid arthritis and the adult respiratory distress syndrome (ARDS).