The effect of intravascular neutrophil chemotactic factors on blood neutrophil and platelet kinetics

Intravenous infusion of an analogue (f-met-leu-phe [FMLP]) of a bacterial-derived polymorphonuclear leukocyte (PMNL) chemotactic factor, or of the complement-derived chemotactic stimulus, zymosan-activated plasma (ZAP, containing C5ades Arg) into rabbits induces acute PMNL margination in the pulmonary vasculature. This process also occurs during hemodialysis and the adult respiratory distress syndrome. The pulmonary PMNL sequestration is accompanied by thrombocytopenia. Because of the role platelets and PMNLs play in hemostasis and defense against infection, we studied the fate of these blood elements following sequestration induced by chemotactic factors. By employing 111In-labelled platelets and external radioisotope scanning, platelets were found to sequester in the pulmonary vasculature during FMLP infusion. Simultaneous 51Cr PMNL and 111In-platelet studies showed that following sequestration, PMNLs returned to the circulation and disappeared with a normal half-life (T1/2) whereas the T1/2 of the platelets was markedly shortened (T1/2 of control = 49 +/- 3.0 hr; FMLP or ZAP infused T1/2 = 27 +/- 2.7 hr). Infusion of platelet-activating factor (PAF) induced PMN and platelet sequestration with similar abnormalities in platelet kinetics. Studies with 51Cr- and 14C-serotonin-labelled platelets showed that platelets did not release serotonin during FMLP, ZAP, or low dose PAF-induced sequestration. In contrast to platelet survival, platelet size, platelet aggregation responses, and platelet glycoproteins were not affected by transient sequestration. These results indicate that during PMNL margination induced by relatively "pure" PMNL stimuli such as FMLP, platelets may reversibly marginate and subsequently be cleared at an accelerated rate. The reason for accelerated platelet clearance is not a result of circulating platelet aggregates or detectable proteolytic modification of membrane glycoproteins. Such altered platelet kinetics may contribute to thrombocytopenia during sepsis, the adult respiratory distress syndrome, and other states in which excess PMNL margination occurs.     

A neutrophil chemotactic factor present inH. pylori but absent inH. mustelae

This study was designed to compare the capabilities ofHelicobacter pylori andHelicobacter mustelae to generate neutrophil chemotactic activity (NCA)in vitro. H. pylori andH. mustelae were grown in parallel cultures under identical conditions. The cultures were washed and transferred to saline solution for 3 hr to avoid detecting nonspecific chemotactic activity from culture media. Supernatants were subjected to size-exclusion HPLC. All peaks from HPLC were collected and assayed for NCA. Peaks having significant NCA were subjected to gel electrophoresis.H. pylori generated 85.9±1.7% NCA compared to only 41.6±2.5% forH. mustelae (P<0.001). The HPLC peak containing the highest NCA fromH. pylori revealed a band on gel electrophoresis at approximately 10.5 kDa. This band was not present on gels fromH. mustelae. We conclude thatH. pylori produces a neutrophil chemotactic factor lacking fromH. mustelae. This offers an explanation for the histologic difference between gastritides caused by these organisms.Presented in part at the American Gastroenterologic Association in New Orleans, May 1991.This work was supported by a VA MERIT grant and Department of Surgery research funding.     

Extraintestinal heterotopic gastric tissue simulating acute appendicitis

We describe the case of a 68-year-old otherwise healthy male who presented to our emergency room with signs and symptoms of acute appendicitis. Exploratory surgery revealed a normal appendix. Further examination revealed an enlarged lymph node-like mass of tissue near the appendix, in the ileocecal mesentery. This mass was removed and was found to be inflamed heterotopic gastric tissue. Although reports of heterotopic gastric tissue in the literature are common, we believe that this case represents the first report of inflamed heterotopic gastric tissue simulating appendicitis.     

An acquired cell-directed inhibitor of neutrophil chemotaxis and hypogammaglobulinemia.

An unusual combination of host defense abnormalities was demonstrated in an adult male with recurrent pulmonary infections due to a variety of microorganisms. Polymorphonuclear neutrophil chemotaxis was defective. Other neutrophil and T-lymphocyte function tests were normal. The patient's serum also showed a severe deficiency of IgG, no detectable IgA, IgM, or IgD, and increased IgE. The chemotactic defect was shown to be due to a cell-directed inhibitor in the patient's serum. The effect of the inhibitor on chemotaxis could be antagonized by factors in normal serum. The chemotaxis defect persisted for several months, but eventually returned to normal.     

Intrinsic neutrophil defects in a child with impaired neutrophil chemotaxis and immunodeficiency

A boy with recurrent pyogenic infection was found to have occasional neutropenia, defective neutrophil chemotaxis, hypogammaglobulinemia with increased IgM, and impaired cellular immunity. The T and B lymphocytes were defective in IgG production in vitro. Ultrastructure of the neutrophils was normal. The marrow cells formed normal numbers of granulocytic colonies in culture, but the colonies were apparently small in size. The levels of colony-stimulating activity were normal. The lymphocytes did not impair granulopoiesis of control marrow cells. These data indicate that the neutropenia and defective neutrophil chemotaxis are due to the intrinsic neutrophil defects and are not secondary to T and/or B lymphocyte dysfunctions in the patient.     

胃癌组织中CTGF蛋白表达及其临床意义

目的探讨结缔组织生长因子（CTGF）蛋自在胃癌发生、发展中的作用。方法采用免疫组化法检测10份正常胃黏膜组织、50份胃癌组织及其癌旁组织中CTGF蛋白表达情况。结果胃癌组织中CTGF阳性表达高于癌旁组织及正常胃黏膜组织,P〈0．05;癌组织CTGF阳性表达率明显高于正常黏膜组织（P〈0．01）,CTGF的高表达与胃癌分化程度、淋巴结转移密切相关（P均〈0．05）;与肿瘤浸润的深度无明显关系。结论CTGF蛋白可作为胃癌前病变及胃癌早期诊断和预后判断的指标。     

Release of chemoattractants and neutrophil activation in acute myocardial infarction immediately after successful recanalization of the infarct-related vessel by angioplasty

The study investigated inflamatory responses in evolving myocardialinfarction. Fifteen patients with acute myocardial infarction,who had undergone balloon recanalization of the infarct-relatedcoronary artery within 4 h after onset of symptoms, were examined.Blood samples were obtained through the guiding catheter andfrom the pulmonary artery before and immediately after successfulrecanalization. After recanalization, plas from the pulmonaryartery was 47% (quartiles: l9%, 78; P =0·001) more chemotacticto neutrophils from normal donors than before recanalization.Furthermore, significant changes in neutrophil function werefound in the pulmonary artery. Compared to the values beforerecanalization, the nitroblue tetrazolium score rose by 31%(quartiles: 4%, 37% P=0·003), FMLP-stimulated superoxideanion production by 10% (quartiles: 0%, 39% P=0·020),and chemotaxis by 46% (quartiles: 0%, 81%, P=0·011),while neutrophil filterability decreased by 28% (quartiles:15%, 47%; P=0·010). No significant changes in neutrophilparameters were found in the arterial blood The study indicatesthat chemoattractants are released in the early reperfusionperiod of evolving myocardial infarction. These chemoattractantsmay act as inflammatory mediators causing neutrophil activation.     

Suppression of blood monocyte and neutrophil chemotaxis in acute human malaria

Summary The host response to Plasmodia includes the production of enlarged populations of peripheral blood monocytes and tissue macrophages in the spleen and the liver. Since the hyperplasia of the mononuclear phagocyte system is believed to arise as a consequence of an enhanced blood monocyte influx, we tested monocyte chemotactic responsiveness in 19 patients with acute primary attack malaria. In addition, the neutrophil chemotaxis was measured in 12 patients. Before the initiation of antimalarial treatment a significant depression of monocyte chemotaxis was observed in approximately half of the patients when compared with healthy control subjects. The depression was found in Plasmodium falciparum malaria as well as in P. vivax or P. ovale malaria patients. The defective responsiveness was not receptor specific, since the responses towards casein and zymosan activated serum proved to be equally suppressed. The monocyte chemotaxis was followed in 14 of the patients, during treatment and after complete recovery. After 3 days of treatment the response had improved in most of the patients, and after 7 days all patients had a normal monocyte chemotaxis, which remained normal after one month. No significant differences between P. falciparum and P. vivax/ovale malaria was observed with respect to blood monocyte chemotactic responsiveness. Neutrophil chemotaxis in patients with P. falciparum infections was similarly suppressed before treatment (54% of controls), was still defective after 3 days of treatment, and nearly normalized after 7 days (87% of controls). Furthermore, monocyte phagocytic and candidacidal activities were assessed in the same patients on admission and during the follow-up. In contrast to chemotaxis, these functions were normal in all of the patients whenever measured. In conclusion, not all cell functions were altered in concert, and the previously unreported suppression of chemotactic migration might reflect a change in blood leucocyte subpopulations, deactivation in vivo or a direct suppressive effect of Plasmodia induced products.     

Effects of high-dose granulocyte colony-stimulating factor on neutrophil functions

We evaluated the effects of high-dose recombinant human granulocyte colony-stimulating factor (rhG-CSF) therapy on N-formyl-methionyl-leucyl-phenylalanine (FMLP)-induced chemotaxis and superoxide (O ⁻₂) production in neutrophils from four patients with aplastic anaemia. The FMLP-induced chemotaxis and O ⁻₂ production in the neutrophils of all four patients were normal before the rhG-CSF treatment. After the administration of high-dose rhG-CSF, chemotaxis in agarose was decreased, adherence and O ⁻₂ production were enhanced in all the patients. An excessive increase of neutrophils with augmented adhesiveness and oxygen radical production may be harmful. Care should be taken in regard to neutrophil toxicity when high-dose G-CSF is used clinically.     

Isoproterenol-induced gastric mucosal protection from bile acid

Topical isoproterenol is a potent protective agent against bile acid-induced gastric mucosal injury in hypotensive and normotensive rats. This study was undertaken to ascertain what role endogenous prostaglandins and gastric mucosal blood flow play in isoproterenol-induced protection. Accordingly, anesthetized, fasted rats were given the cyclooxygenase inhibitor, indomethacin (5 mg/kg subcutaneously), 30 min prior to topical pretreatment with 3 ml of intragastric saline, isoproterenol (3 M), or 16,16-dimethyl prostaglandin E₂ (3 M) for 15 min. Gastric injury was induced with topical 5 mM acidified taurocholate and damage assessed by measuring net transmucosal ion fluxes, the appearance of DNA into the gastric lumen, and histology of the gastric epithelium. In a separate set of experiments, the effects of topical isoproterenol on gastric mucosal blood flow (laser Doppler flowmetry) and luminal PGE₂ concentrations (¹²⁵I radioimmunoassay) were examined. Pretreatment with topical isoproterenol or 16,16-dimethyl prostaglandin E₂ significantly decreased bile acid-induced net luminal ion fluxes and DNA accumulation, suggesting mucosal protection. The protective effect of isoproterenol, but not 16,16-dimethyl prostaglandin E₂, was negated by indomethacin (corroborated by histology). Further, isoproterenol did not significantly alter gastric mucosal blood flow, but did augment luminal PGE₂ concentrations, an effect also abolished by indomethacin. Thus, isoproterenol appears to protect the gastric mucosa from the damaging effects of bile acid through a mechanism that requires the synthesis and release of cytoprotective endogenous prostaglandins.     

老年患者幽门螺杆菌感染与胃炎活动性相关性分析

目的探讨老年患者幽门螺杆菌(Hp)感染与胃炎活动性的相关性。方法回顾性地分析2014年1月至2014年6月于北京老年医院接受胃镜及~(13)C呼气试验检查的良性上消化道疾病患者278例,依据年龄分为年龄≥60岁(老年组)111例和年龄60岁(非老年组)167例,分别观察两组患者Hp感染情况及胃黏膜组织中性粒细胞浸润与Hp感染的关系。结果老年组与非老年组比较,Hp感染率分别为27.0%(30/1 11)和36.5%(61/167),差异无统计学意义(P0.05);中性粒细胞浸润率分别为18.9%(21/111)和29.3%(49/118),差异无统计学意义(P0.05);Hp阳性和Hp阴性患者中性粒细胞浸润分别为70.3%(64/91)和3.2%(6/187),差异有统计学意义(P0.05);Hp阳性患者老年组和非老年组中性粒细胞浸润分别为63.3%(19/30)和73.8%(45/61),中性粒细胞浸分级(轻、中、重)分别为26.3%vs 17.8%,57.9%vs 71.1%,15.8%vs11.1%,差异均无统计学意义(P0.05)。结论胃黏膜急性炎症与Hp感染相关,急性炎症分级与感染年龄无关。     

Morphologic and functional heterogeneity of chronic neutropenia of childhood with normal neutrophil colony formation in vitro

In order to obtain further knowledge of chronic neutropenia of childhood, we studied nine neutropenic infants six to ten months of age by in vitro techniques, including bone marrow culture, electron microscopy, and chemotaxis assay. Eight of the nine patients had a benign clinical course and the bone marrow aspirates showed a reduced number of segmented neutrophils. The ninth patient had a moderately severe course and the bone marrow showed maturation arrest at the promyelocyte stage. Bone marrow cultures demonstrated that the in vitro neutrophil colony formation and production of colony-stimulating activity were normal in all of the eight patients studied. Neutrophils from one of the nine patients had ultrastructural abnormalities such as a decrease in number of primary and secondary granules and the presence of myelin figures in primary granules. Neutrophil chemotaxis was defective in three of the nine patients. All of the six patients in whom the neutrophil colony formation in agar, the ultrastructure of neutrophils, and neutrophil chemotaxis were normal recovered from the neutropenia between 11 and 30 months of age. These in vitro parameters appear to be useful for evaluating chronic neutropenia of childhood.     

胃黏膜炎症和肠上皮化生与幽门螺杆菌关系的远期观察

[目的]远期追踪幽门螺杆菌(Hp)相关胃炎及Hp阴性的胃炎胃黏膜炎症和肠上皮化生(IM)在病程演变中的关系.[方法]经胃镜检查确诊的Hp阳性胃炎86例(A组),Hp阴性的胃炎92例(B组),对照观察两组5年前后的逆转变化,胃黏膜炎症和IM的程度积分.[结果]5年后A组86例中Hp阳性者61例(70.9%)、转阴者25例(29.1%);5年后两组Hp阳性者、5年前后的炎症程度积分差异无统计学意义;B组Hp阴性者、A组Hp阳性者5年前后比较差异无统计学意义;5年后B组中Hp仍阴性者与A组Hp仍阳性者,其胃黏膜炎症和IM积分比较差异有统计学意义(P＜0.01).[结论]Hp在胃黏膜内存在的时间越长,其炎症和IM的程度越重,发生率也增加,而Hp阴性的胃炎和Hp阳性胃炎转阴后其炎症和IM的程度及发生率均有下降.     

Inflammatory mediators involved in the progression of the metabolic syndrome

The metabolic syndrome is often associated with type 2 diabetes mellitus, dyslipidemia, atherosclerosis, hypertension, steatosis of the liver and other organs, as well as hypertension, type 2 diabetes mellitus, and atherosclerosis. Recent studies have implicated a number of inflammatory mediators including cytokines, adipokines and eicosanoids in the inflammatory responses that accompany the metabolic syndrome. Measurements of the circulating levels of the inflammatory molecules that accompany this syndrome might provide leads to therapeutic approaches to modulate the inflammatory responses and thereby alter disease progression. In this review, we summarize recent studies on classical and newer inflammatory mediators in the pathogenesis of the metabolic syndrome in humans and experimental models.     

Clinical study of 31 patients with primary gastric mucosa-associated lymphoid tissue lymphoma

BACKGROUND: The purpose of the present paper was to investigate the clinical, endoscopic and histological features of 31 patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma to enable correct, early stage diagnosis. METHODS: A retrospective study was undertaken of 31 patients with gastric MALT lymphoma. The cases were examined immunohistologically with anti-CD(20CY) and CD(45RO) antibodies for further diagnosis. Helicobacter pylori infection was also detected with modified Giemsa staining. RESULTS: Patients with MALT lymphoma were aged between 22 and 73 years (mean, 45.0 years), and the male:female ratio was 11:20. The patients presented with non-specific symptoms, but chronic epigastric pain was the common symptom in a large proportion of the cases. The gastric smaller curvature was involved in 83.9% of cases (26/31) and in 13/31 cases (41.9%) it was confined the antrum. Under endoscopy, large and deep ulcers were similar to cancers in the majority of patients. Only 29.0% of patients were diagnosed by endoscopy on first examination. CD(20CY) were expressed in all cases and CD(45RO) expressed in only one case among 10 cases of indefinite diagnosis. Helicobacter pylori infection was found in 87.1% of patients. CONCLUSIONS: These findings suggest that primary gastric MALT lymphoma has unique clinical, endoscopic and histological features. The diagnosis for primary gastric MALT lymphoma was delayed not only due to the non-specific symptoms but also due to lack of attention to its features. Endoscopy and submucosal multiple biopsy were the principal diagnostic tools in patients with gastric MALT lymphoma. CD(20CY) and CD(45RO) immunological staining are recommended, especially for patients with indefinite diagnosis of gastric MALT lymphoma.     

Secretory leukocyte protease inhibitor inhibits neutrophil apoptosis

Background and objective: The secretory leukocyte protease inhibitor (SLPI) is a major anti‐elastase barrier at the epithelial surfaces of upper respiratory tract. In addition to its anti‐protease activity, SLPI has been shown to express anti‐bacterial, anti‐viral and anti‐inflammatory properties. Methods: We measured SLPI concentration in nasal lavage fluid of healthy volunteers after challenge with endotoxin (LPS) and evaluated SLPI effects in vitro on neutrophil chemotaxis, adhesion, cytokine (IL‐8) release and apoptosis. Results: SLPI concentration in nasal lavage (n = 9) 2, 6 and 24 h after the challenge with LPS (25 µg) increased from 32% to 238% compared with baseline (226 ± 71 ng/mL). In vitro, SLPI (20–80 µg/mL) induced neutrophil chemotaxis (sixfold, P < 0.001) and decreased neutrophil apoptosis by 73% (P = 0.006), relative to controls. However, SLPI had no affect on IL‐8 release or neutrophil adhesion to fibronectin. SLPI‐positive immunoreactivity was co‐localized with neutrophils in lung specimens from patients with COPD. Conclusions: Our findings indicate upregulation of SLPI in response to LPS in nasal secretions and show anti‐apoptotic effects of SLPI in primary human neutrophils suggesting a new role of SLPI during neutrophilic inflammation.     

胃溃疡大鼠胃粘膜血流量与泌酸变化的研究

用手术将十二指肠内容物持续胃内反流制成大鼠胃溃疡及经转流后的溃疡愈合模型进行研究。结果表明,溃疡组于胃窦小弯侧可见8.84±3.08(m~2)~(-3)的慢性溃疡形成,并显示胃粘膜血流量降低,G细胞密度、壁细胞数增加。溃疡愈合组经转流后大部分溃疡已愈合,G细胞密度、壁细胞数降低,粘膜血流量增加。本实验提示,泌酸细胞增多,泌酸量增加和胃粘膜缺血可能是溃疡形成的重要因素,增加胃粘膜的血液供应,降低胃酸分泌可促进溃疡愈合。     

The function in vitro of macrophages from the intestinal mucosa of patients with Crohn's disease: An association between chemotactic migration and granulomata

The chemotactic migration in vitro of intestinal macrophages and peripheral blood monocytes has been assessed in patients with Crohn's disease, ulcerative colitis, and miscellaneous intestinal diseases. In all groups, the chemotaxis of peripheral blood monocytes was similar to that of healthy subjects. Intestinal macrophages migrated similarly to autologous monocytes in patients with ulcerative colitis and in the miscellaneous group. In contrast, intestinal macrophages from patients with Crohn's disease exhibited a wide range of chemotaxis from markedly suppressed to normal. This variation was independent of drug treatment and the degree of inflammation present. However, patients in whom granulomata were not present exhibited a significant depression of chemotaxis compared with those with granulomata, with disease controls (ulcerative colitis patients), and with the miscellaneous group. Such a difference was not reflected in monocytes from autologous peripheral blood. These findings indicate the presence of local mucosal suppressive factors in some patients with Crohn's disease and could suggest that the diminished ability of macrophages to accumulate in a focus of inflammation may be an underlying mechanism for the failure to form granulomata in these patients.     

Effects of obstructive jaundice on neutrophil production and acquisition of chemotactic activity in the bone marrow

Background and Aims:  Increased numbers and enhanced functions of peripheral neutrophils have been observed in obstructive jaundice. However, the effects of obstructive jaundice on the bone marrow, that is neutrophil production and acquisition of neutrophil chemotactic activity, have been poorly understood. In the present study, differentials of bone marrow cells and chemotactic activity of bone marrow neutrophils were evaluated in bile duct-obstructed rats.
Methods:  Male Wistar rats underwent either bile duct obstruction for 10 days or bile duct obstruction for 4 days followed by 6 days' internal biliary drainage. Differentials of peripheral blood and bone marrow cells were sequentially determined. Chemotactic activity of peripheral and bone marrow neutrophils was evaluated with a modified Boyden method using interleukin-8 (recombinant rat Gro-β) as a chemoattractant.
Results:  Numbers of peripheral neutrophils significantly increased after bile duct obstruction. Significant increases in the myeloid/erythroid (M/E) ratio of bone marrow cells were observed after bile duct obstruction. The neutrophil proliferative pool (promyelocytes and myelocytes) increased initially, followed by an increased neutrophil storage pool (metamyelocytes, bands, and segmented neutrophils). The M/E ratio as well as the neutrophil proliferative and storage pools normalized after internal biliary drainage. Chemotactic activity was enhanced in both peripheral and bone marrow neutrophils after bile duct obstruction, and enhanced chemotaxis was alleviated with internal biliary drainage.
Conclusion:  The present results strongly suggest the principal role of the bone marrow in increasing the number of neutrophils and their chemotactic activity during obstructive jaundice.