Event Abstract

ROLE OF MACROPHAGES REACTION IN PATHOGENESIS OF DUODENAL ULCER BLEEDING

  • 1 M. Gorky Donetsk National Medical University, Histology, Cytology and Embryology, Ukraine

Gastroduodenal ulcer bleeding is a common cause of hospital admission and life-threatening medical emergency. Nowadays 20-30% of patients with primary ulcer hemorrhage demonstrate the development of recurrent bleeding independently of drug treatment and endoscopic hemostasis. Recent studies of clinical, laboratory and endoscopic features of peptic ulcers and their complications have revealed the wide list of factors which are associated with this pathology. Current recommendations for the step-wise management of patients with upper gastrointestinal bleeding are based on features such as hemodynamic status, comorbidities, age, laboratory tests and upper endoscopy results. But this approach is not useful to answer the questions why vascular injury in ulcer region is not accompanied by effective hemostasis and ulcer healing in some patients&

Looking for the answers we have focused on assessment of macrophages which are considered as key regulators of inflammation and reparation and tightly associated with hemostasis state. It is a well established fact that macrophages play the pivotal role both in progression of acute inflammation and regeneration initiation. Partly it can be explained by L-arginine cycle activation, with balancing between inducible nitric oxyde synthase and Arginase-1 alternative pathways. The analysis of this option is interesting because of double control of iNOS activity by classic and alternative mechanisms.
In this work we analyzed the role and mechanisms of macrophage dysfunction in patients with different outcome of duodenal ulcer bleeding.

Materials and methods. We analyzed the relation between clinical characteristics, pathomorphology of ulcer margin and periheral blood monocytes state in patients with duodenal ulcers. A cohort study was conducted in 146 patients with a diagnosis of duodenal ulcer bleeding enrolled between January 1, 2010 and June 30, 2012 to state hospital №16 (Donetsk, Ukraine). Patients considered eligible for enrollment were over 18 years of age, suffer from typical symptoms of acute bleeding from duodenal ulcers, confirmed by positive upper gastrointestinal endoscopy. Exclusion criteria were age younger than 18 years or over 75 years, any allergy to established medications, coagulopathy, infarction of myocardium and ischemic stroke in the last 6 months, pregnancy, cirrhosis or use of steroids, a proton pump inhibitors or H2-receptor antagonists in the 2 weeks prior to enrollment in the study. The patients with malignant ulcers or trauma were also excluded. We evaluated patients’ demographic characteristics, time from first bleeding symptoms and hospital admission, comorbidities, drugs taken at the time of admission, clinical manifestation and initial laboratory tests. The morphological observation of marginal ulcer zone of 64 patients with sustained hemostasis (1st group) and 28 patients with recurrent bleeding (2nd group) was performed. The number and distribution of CD68 positive cells were assessed in different regions of duodenal mucosa, including villi, transitional and pericryptal zones. Whole blood for the in vitro study was sampled from patients with peptic ulcer bleeding at the moment of hospital admission before therapy. The iNOS activity in separated peripheral blood monocytes was measured under basal conditions and after incubation with lipopolysaccharide (LPS), 5-hydroxytryptamine (5-HT) and epinephrine in NBT test. Data were collected and analyzed using the statistical package MedCalc version 12.3 (MedCalc Software Inc., 1993–2012). Descriptive statistics were used to analyze and report the data.

Results. Duodenal ulcer bleeding was associated with ischemia and inflammation symptoms in marginal zone of ulcers. The high density of macrophages was observed in villi rather than pericryptal region of duodenal mucosa biopsy in 1st group. Recurrent ulcer bleeding was associated with increase of macrophages number (P = 0.012) predominantly in transitional and perycryptal space. Increase of macrophages number in 2nd group biopsy was accompanied with microcirculatory disturbance and edema, intensive infiltration with neutrophils and alteration of mucosa. To find out the reasons of these morphological features we analysed the monocytes state by iNOS activity in vitro. It has revealed that increased recruitment of macrophages in duodenal mucosa was associated with higher basal activity of iNOS. This fact can reflect the initiation of proinflammatory activation of peripheral blood monocytes, while LPS-stimulated activity of the enzyme was restricted. Moreover, proinflammatory activation of monocytes and increase of duodenal mucosa macrophages in patients with ulcer bleeding were associated with dysregulation of monocytes by humoral and coagulation factors. Macrophages accumulation around bottoms of crypts in biopsy of 2nd group patients correlated with monocytes iNOS activity under basal conditions (P = 0,001), and after incubation with epinephrine (P = 0.001) or thrombine (P = 0.02), but not with 5-HT. The hypersensitivity to alternative regulators can reflect their role in monocytes-macrophages hyperactivation under the bleeding.

Conclusion. Proinflammatory activation of monocytes and increase of macrophages recruitment into duodenal mucosa were associated with dysregulation of L-arginine metabolism and its modulation by humoral and coagulation factors.

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Keywords: Macrophages, inducible nitric oxide synthase, Duodenal Ulcer, bleeding, healing plants

Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.

Presentation Type: Abstract

Topic: Immune-mediated disease pathogenesis

Citation: Sulaieva ON (2013). ROLE OF MACROPHAGES REACTION IN PATHOGENESIS OF DUODENAL ULCER BLEEDING. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00622

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Received: 11 Jun 2013; Published Online: 22 Aug 2013.

* Correspondence: Mrs. Oksana N Sulaieva, M. Gorky Donetsk National Medical University, Histology, Cytology and Embryology, Donetsk, Ukraine, oksana.sulaeva@dsmu.edu.ua

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