Mesenteric Tissue Research Articles

Ultrasonic features of pediatric eosinophilic gastroenteritis of children

Objective To summarize the manifestation of pediatric eosinophilic gastroenteritis by ultrasound and discuss the diagnostic value of ultrasonography in pediatric eosinophilic gastroenteritis. Methods The ultrasonic appearances of 31 cases of pediatric eosinophilic gastroenteritis confirmed by clinics and pathology were reviewed and analyzed. Results Nineteen of 31 cases were observed in association with eosinophilic infiltration of other organs which were diagnosed as idiopathic hypereosinophilic syndrome. Eosinophilic cystitis was the most common among the complications(89.4%, 17/19). Twelve of 31 cases were diagnosed as eosinophilic gastroenteritis without complications. The endoscopic appearances of eosinophilic gastroenteritis were nonspecific which include erythematous, hyperemia edema, and partiality erosion changes. Endoscopy demonstrates increased numbers of eosinophils in the propria of stomach and the duodenum. Ultrasound features of the gastroenteritis appeared diffuse or the parts of gastrointestinal tract. The most common sites of eosinophilic gastroenteritis were the stomach and duodenum.Involvement of muscle layer and serosal layer showed wall thickening of cyclic annular and uniformity. Ultrasound might show nodular or irregular thickening of the folds in the gastric antrum when the submucosa were thickening. The mucosal layer involvement was not easy to be found by ultrasound. The echo of serous layer and submucosa associated with the disease stage. The thickening of surrounding omentum and mesenteric tissue, echo enhancement and nonspecific hyperplastic mesenteric lymph nodes infiltrated with eosinophils might be present.Eosinophilic ascites could often be detected. Conclusions Ultrasound has obvious advantages in the diagnosis of pediatric eosinophilic gastroenteritis, and the ultrasonic changes of pediatric eosinophilic gastroenteritis are characterized. Ultrasonography can provide the possible diagnosis when combined with inflammatory of other organs, especially cystitis inflammatory changes. Key words: Ultrasonography; Pediatric; Eosinophilic gastroenteritis

Emergency ultrasonography of the gastrointestinal tract of children.

Ultrasonography (US) is widely used to evaluate most body parts in pediatric patients because it is simple, noninvasive, easy to use, and applicable in a wide variety of clinical situations. US is the modality of choice for the initial evaluation of acute abdominal pain in pediatric patients because of their small body habitus and the presence of less fat tissue in the abdominal wall and peritoneal cavity. The most important factor in performing pediatric emergency US is the graded compression technique and selection of the proper transducer. The careful evaluation of bowel wall thickening combined with ancillary findings such as fluid collection, increased echogenicity of the mesenteric fat tissue, enlarged lymph nodes, hyperemic bowel changes, and abnormal bowel peristalsis can increase the diagnostic capability of US.

The Use of the EndoGrab™ Port-Free Endocavity Retractor in Single-Incision Laparoscopic Right Hemicolectomy.

The EndoGrab™ Port-Free Endocavity Retractor is an internally anchored retracting device that enables surgeons to reduce not only the number of ports and incisions but also the number of assistant surgeons. Our institution performs single-incision laparoscopic colectomy (SILC) as a routine procedure. Forty-nine patients underwent a single-incision laparoscopic right hemicolectomy. In this procedure, we use this retractor to the mesenteric tissue, including the ileocolic vessels and the mesentery of the transverse colon, and overcame the technical problems related to SILC and showed excellent short-term outcomes. To perform SILC safely while maintaining the minimal invasiveness and the quality, the use of this retractor is essential, especially in difficult situations, such as an unfavorable visual field when performing a lymph node dissection around the middle colic vessels in right hemicolectomy.

Sigmoid Diverticulitis Mimicking Acute Appendicitis in Right-Sided Descending and Sigmoid Colon: A Case Report

Introduction: Acute abdominal pain in the lower-right quadrant can be misdiagnosed as acute appendicitis and may be caused by anatomic variations of the intra-abdominal organs in rare cases. Anatomical variations in the position and morphology of the sigmoid colon should be considered by clinicians and radiologists to avoid misdiagnosis and unnecessary surgical procedures.Case Report: A 54-year-old man was admitted to our emergency department complaining of abdominal pain in the lowerright quadrant, nausea, vomiting, and fever for 2 days. Physical examination revealed local rebound tenderness on the lowerright quadrant and a temperature of 38°C. Abdominal ultrasound showed that the intestinal loops were thickened and the surrounding mesenteric tissue was edematous in the right abdominal quadrant. Abdominal computed tomography was performed after a bolus administration of intravenous contrast material, and sigmoid colon position anomalies and diverticulitis were observed. The patient was treated medically, and diverticulosis was confirmed by colonoscopy. Conclusion: Clinical evaluation and ordered appropriate imaging methods by the emergency specialist is important in patients with abdominal pain on the lower-right quadrant who are admitted to the emergency department. Thus, rare anatomical variations mimicking acute appendicitis can be diagnosed accurately, and patients can be protected from undergoing unnecessary surgeries

Radiographic and Ultrasonographic Findings in Three Surgically Confirmed Cases of Small Intestinal Ischemia Related to Mesenteric Volvulus or Intestinal Torsion in Dogs

This case report describes the radiographic and ultrasonographic findings of three surgically confirmed cases of mesenteric volvulus or intestinal torsion in dogs. In all three cases, ultrasonographic findings included segmental ileus and absent or markedly reduced peristalsis of the affected small intestine, and partial loss of wall layering with increased overall echogenicity of the intestinal wall, but with normal to mildly increased wall thickening. No blood flow was detected in the affected small intestinal wall when assessed with colour Doppler. A moderate amount of peritoneal effusion was also detected with hyperechoic omental and mesenteric fat tissue throughout the peritoneal cavity. Few reports describe ultrasonographic findings of small intestinal ischemia in small animals. In all three cases presented here, ultrasound was helpful in demonstrating typical intestinal wall changes and helped to obtain the correct diagnosis of ischemic disease of the small intestine.

Role of visceral fat in colonic inflammation: from Crohn's disease to diverticulitis.

The composition of activated adipose tissue with adipocytes secreting a broad spectrum of immune-modulatory adipokines next to adipose tissue-derived stromal cells and professional immune effector cells in the visceral fat creates a complex network of inflammatory processes shaping local immune responses in the adjacent inflamed intestinal mucosa. In Crohn's disease a particular phenomenon called 'creeping fat' can be observed. Here the hyperplastic mesenteric fat tissue not only grows around inflamed small intestinal segments but also furthermore affects the regulation of the mucosal immune system. Diverticular disease is highly prevalent in the western world but the knowledge about its immunopathology remains incomplete. Interestingly, adipose tissue also frequently covers the basolateral site of inflamed diverticula, hence locally reflecting the phenomenon seen in Crohn's disease. This review aims to summarize the current knowledge in which measures this intraabdominal fat participates in the regulation of intestinal inflammation with a particular focus on differences and possible parallels in Crohn's disease and diverticulitis. The available data allow for suggesting that each inflamed diverticula mechanistically reflects Crohn's disease on a miniature scale.

Mast cells and histamine are triggering the NF-κB-mediated reactions of adult and aged perilymphatic mesenteric tissues to acute inflammation.

This study aimed to establish mechanistic links between the aging-associated changes in the functional status of mast cells and the altered responses of mesenteric tissue and mesenteric lymphatic vessels (MLVs) to acute inflammation. We used an in vivo model of acute peritoneal inflammation induced by lipopolysaccharide treatment of adult (9-month) and aged (24-month) F-344 rats. We analyzed contractility of isolated MLVs, mast cell activation, activation of nuclear factor-κB (NF-κB) without and with stabilization of mast cells by cromolyn or blockade of all types of histamine receptors and production of 27 major pro-inflammatory cytokines in adult and aged perilymphatic mesenteric tissues and blood. We found that the reactivity of aged contracting lymphatic vessels to LPS-induced acute inflammation was abolished and that activated mast cells trigger NF-κB signaling in the mesentery through release of histamine. The aging-associated basal activation of mesenteric mast cells limits acute inflammatory NF-κB activation in aged mesentery. We conclude that proper functioning of the mast cell/histamine/NF-κB axis is necessary for reactions of the lymphatic vessels to acute inflammatory stimuli as well as for interaction and trafficking of immune cells near and within the collecting lymphatics.

Aging is associated with impaired angiogenesis, but normal microvascular network structure, in the rat mesentery.

Using a multidimensional approach, we present evidence supporting that aged microvascular networks display vessel density and patterning similar to adult networks despite also being characterized by a decreased capacity to undergo angiogenesis. Thus, vessel loss is not necessarily a characteristic of aging.

Lymphoid Aggregates Remodel Lymphatic Collecting Vessels that Serve Mesenteric Lymph Nodes in Crohn Disease

Early pathological descriptions of Crohn disease (CD) argued for a potential defect in lymph transport; however, this concept has not been thoroughly investigated. In mice, poor healing in response to infection-induced tissue damage can cause hyperpermeable lymphatic collecting vessels in mesenteric adipose tissue that impair antigen and immune cell access to mesenteric lymph nodes (LNs), which normally sustain appropriate immunity. To investigate whether analogous changes might occur in human intestinal disease, we established a three-dimensional imaging approach to characterize the lymphatic vasculature in mesenteric tissue from controls or patients with CD. In CD specimens, B-cell-rich aggregates resembling tertiary lymphoid organs (TLOs) impinged on lymphatic collecting vessels that enter and exit LNs. In areas of creeping fat, which characterizes inflammation-affected areas of the bowel in CD, we observed B cells and apparent innate lymphoid cells that had invaded the lymphatic vessel wall, suggesting these cells may be mediators of lymphatic remodeling. Although TLOs have been described in many chronic inflammatory states, their anatomical relationship to preestablished LNs has never been revealed. Our data indicate that, at least in the CD-affected mesentery, TLOs are positioned along collecting lymphatic vessels in a manner expected to affect delivery of lymph to LNs.

Chronic saponin treatment attenuates damage to the pancreas in chronic alcohol-treated diabetic rats

BackgroundChronic heavy alcohol consumption may raise the risk of developing type 2 diabetes mellitus. Saponins inhibit apoptosis of pancreatic islet cells and reduce lipid parameters. The present study was designed to investigate the effect of saponin on chronic ethanol-treated diabetic rats. MethodsLong–Evans Tokushima Fatty (LETO) and Otsuka Long–Evans Tokushima Fatty (OLETF) rats were pair-fed a Lieber–DeCarli diet with and without 5% ethanol for 12 wks. Two weeks after starting the pair-feeding with the Lieber–DeCarli diet, intraperitoneal injection of saponin was performed for 10 wks. To perform the experiments, rats were divided as follows: LETO-Control (LC), LETO-Ethanol (LE), LETO-Ethanol-Saponin (LES), OLETF-Control (OC), OLETF-Ethanol (OE), and OLETF-Ethanol-Saponin (OES). ResultsThe weights of epididymal and mesenteric fat tissue in LES and OES rats were the lightest from among the LETO and OLETF groups, respectively. The secretion of alanine aminotransferase and cholesterol in OES rats decreased significantly compared to their secretion in OC and OE rats, respectively. The islets of the pancreas in LE and OE rats showed clean, unclear, and smaller morphology compared to those of LC, LES, OC, and OES rats. In addition, the expression of insulin in the islets of the pancreas in LC, LES, OC, and OES rats was higher than in LE and OE rats. ConclusionSaponin may not only be helpful in alleviating the rapid progress of diabetes due to chronic alcohol consumption in diabetic patients, but may also show potential as an antidiabetic drug candidate for diabetic patients who chronically consume alcohol.

Macrophage alterations within the mesenteric lymphatic tissue are associated with impairment of lymphatic pump in metabolic syndrome.

The intrinsic lymphatic pump is critical to proper lymph transport and is impaired in models of the MetSyn. Lymphatic contractile inhibition under inflammatory conditions has been linked with elevated NO production by activated myeloid-derived cells. Hence we hypothesized that inhibition of the MLV pump function in MetSyn animals was dependent on NO and was associated with altered macrophage recruitment and polarization within the MLV. We used a high fructose-fed rat model of MetSyn. Macrophage polarization was determined by whole mount immunofluorescence in mesenteric neurovascular bundles based on expression of CD163, CD206, and MHCII. We also utilized isolated vessel isobaric preparations to determine the role for elevated NO production in the inhibition of MLV contractility. Both LECs and LMCs were used to assess the cytokines and chemokines to test how the lymphatic cells response to inflammatory conditions. Data demonstrated a greater accumulation of M1-skewed (CD163+ MHCII+ ) macrophages that were observed both within the perivascular adipose tissue and invested along the lymphatic vessels in MetSyn rats when compared to control rats. LECs and LMCs basally express the macrophage maturation polarization cytokines monocyte colony-stimulating factor and dramatically up regulate the M1 promoting cytokine granulocyte/monocyte colony-stimulating factor in response to lipopolysaccharide stimulation. MetSyn MLVs exhibited altered phasic contraction frequency. Incubation of MetSyn MLVs with LNAME or Glib had a partial restoration of lymphatic contraction frequency. The data presented here provide the first evidence for a correlation between alterations in macrophage status and lymphatic dysfunction that is partially mediated by NO and KATP channel in MetSyn rats.

English

Anti-allergics, including mast cell stabilizers, are used together with other anti-inflammatory drugs in the management of asthma, so as to prevent the release of pre-formed inflammatory mediators upon allergen exposure. This study was aimed at investigating the mast cell stabilizing and anti-anaphylactic effects of a 70% hydro-ethanolic extract of Scoparia dulcis (SDE) in murine models upon exposure to a known allergen. In vitro cytological and histological studies were conducted on guinea-pigs peritoneal cells and mesenteric tissues, respectively, to establish mast cell stabilization effect of the extract on compound 48/80-induced mast cell degranulation. The ability of SDE to protect mice against anaphylactic shock induced by compound 48/80 was also assessed. Preliminary phytochemical analysis was conducted on the extract using standard phyto-analytic procedures. Phytochemical screening showed the presence of tannins, alkaloids, glycosides, saponins, steroids and phenolic compounds. SDE showed significant inhibition (P ≤ 0.001) against compound 48/80-induced degranulation in both the peritoneal and mesenteric mast cells of guinea-pigs (comparable to sodium cromoglycate and ketotifen fumarate). SDE also delayed the onset of symptoms of anaphylaxis in mice induced with compound 48/80, as well as reduced their mortality rate. The hydro-ethanolic extract of S. dulcis has significant mast cell stabilizing and anti-anaphylactic activities; making it a better adjunct in asthma management.   Key words: Anti-allergenic, Mast cell stabilization, Anti-anaphylactic, Compound 48/80, Scoparia dulcis.

α-Phellandrene, a cyclic monoterpene, attenuates inflammatory response through neutrophil migration inhibition and mast cell degranulation

AimsWe aimed to investigate the modulating effect of α-phellandrene on neutrophil migration and mast cell degranulation processes. Main methodsMale Wistar rats or Swiss mice were treated p.o. with vehicle (3% Tween 80, p.o.), α-phellandrene (50, 100, or 200mg/kg, p.o.), or dexamethasone (0.5mg/kg, p.o.) 1h before carrageenan injection. Then, the neutrophil migration in 6-day-old air pouches or peritoneal cavities. The leukocyte rolling and adhesion were measured in real time and assessed by intravital microscopy. ELISA was used to detect TNF-α and IL-6 in peritoneal lavage. Compound 48/80–induced mast cell degranulation was assessed in mesenteric rat tissues. Key findingsIn all the tested doses, α-phellandrene prevented carrageenan-induced neutrophil accumulation (P<0.05). As detected by intravital microscopy, α-phellandrene also inhibited leukocyte rolling and adhesion, as well as significantly inhibited the production of the pro-inflammatory cytokines TNF-α and IL-6. Moreover, the degranulation of compound 48/80–induced mast cells was also inhibited by α-phellandrene (P<0.001). SignificanceThese results suggest that α-phellandrene plays an important role as an anti-inflammatory agent through neutrophil migration modulation and mast cell stabilization.

Mesenteric panniculitis: review of consecutive abdominal MDCT examinations with a matched-pair analysis.

Background The relationship between mesenteric panniculitis (MP), a benign condition involving adipose mesenteric tissue, and malignancy is still being questioned. Purpose To investigate the prevalence of MP and study its relationship with malignancy. To investigate the 5-year outcome of MP patients for the development of malignancy. Material and Methods Retrospective search for MP reviewing 3054 consecutive multidetector row computed tomography (MDCT) scans. Two radiologists in consensus selected the final MP population. For each MP, two subsequent MDCT scans of patients matched by gender and age. Five-year follow-up data regarding cancer occurrence after index MDCT scans were obtained for the MP and control groups. Comparisons between groups were performed using univariate conditional logistic regression. Results A total of 160 patients had at least three of the five MDCT features defining MP. Sixty-four were excluded owing to disease causing mesenteric infiltration or contiguous neoplastic involvement. The final population included 96 MP and 192 control patients. The prevalence of MP was 3.14%. Most cases of MP were discrete (66.7%), 2.1% were marked. In total, 60.4% and 59.4% of MP and control patients, respectively, had cancer ( P = 0.86). There was no significant association between MP score and presence of cancer ( P = 0.06) nor any relationship between the course of associated cancer and MP evolution. In total, 80/96 MP patients and 50/78 control patients without associated cancer had a 5-year follow-up at least. No significant difference between both groups for new tumor occurrence during follow-up was found ( P = 0.15). Conclusion Our results do not suggest that patients with incidentally found MP should be followed up for early detection of a cancer.

Lysophosphatidic acid does not cause blood/lymphatic vessel plasticity in the rat mesentery culture model.

Understanding the mechanisms behind endothelial cell identity is crucial for the goal of manipulating microvascular networks. Lysophosphatidic acid (LPA) and serum stimulation have been suggested to induce a lymphatic identity in blood endothelial cells in vitro. The objective of this study was to determine if LPA or serum induces blood‐to‐lymphatic vessel phenotypic transition in microvascular networks. The rat mesentery culture model was used to observe the effect of stimulation on blood and lymphatic microvascular networks ex vivo. Vascularized mesenteric tissues were harvested from adult Wistar rats and cultured with LPA or 10% serum for up to 5 days. Tissues were then immunolabeled with PECAM to identify blood vessels and LYVE‐1 or Prox1 to identify lymphatic vessels. We show that while LPA caused capillary sprouting and increased vascular length density in adult microvascular networks, LPA did not cause a blood‐to‐lymphatic phenotypic transition. The results suggest that LPA is not sufficient to cause blood endothelial cells to adopt a lymphatic identity in adult microvascular networks. Similarly, serum stimulation caused robust angiogenesis and increased lymphatic/blood vessel connections, yet did not induce a blood‐to‐lymphatic phenotypic transition. Our study highlights an understudied area of lymphatic research and warrants future investigation into the mechanisms responsible for the maintenance of blood and lymphatic vessel identity.

The Role of the Mesentery in Crohn's Disease: The Contributions of Nerves, Vessels, Lymphatics, and Fat to the Pathogenesis and Disease Course.

Crohn's disease (CD) is a complex gastrointestinal disorder involving multiple levels of cross talk between the immunological, neural, vascular, and endocrine systems. The current dominant theory in CD is based on the unidirectional axis of dysbiosis-innate immunity-adaptive immunity-mesentery-body system. Emerging clinical evidence strongly suggests that the axis be bidirectional. The morphologic and/or functional abnormalities in the mesenteric structures likely contribute to the disease progression of CD, to a less extent the disease initiation. In addition to adipocytes, mesentery contains nerves, blood vessels, lymphatics, stromal cells, and fibroblasts. By the secretion of adipokines that have endocrine functions, the mesenteric fat tissue exerts its activity in immunomodulation mainly through response to afferent signals, neuropeptides, and functional cytokines. Mesenteric nerves are involved in the pathogenesis and prognosis of CD mainly through neuropeptides. In addition to angiogenesis observed in CD, lymphatic obstruction, remodeling, and impaired contraction maybe a cause and consequence of CD. Lymphangiogenesis and angiogenesis play a concomitant role in the progress of chronic intestinal inflammation. Finally, the interaction between neuropeptides, adipokines, and vascular and lymphatic endothelia leads to adipose tissue remodeling, which makes the mesentery an active participator, not a bystander, in the disease initiation and precipitation CD. The identification of the role of mesentery, including the structure and function of mesenteric nerves, vessels, lymphatics, and fat, in the intestinal inflammation in CD has important implications in understanding its pathogenesis and clinical management.

Research Regarding Prelevation and Preparation of Porcine Small Intestinal Submucosa for Corneal Reconstruction in Dogs and Cats

Porcine small intestinal submucosa (SIS) is a natural biomaterial, consist of collagen, proteoglycan glycosaminoglycan, glycoprotein and growth factors. This study was conducted in Surgery Clinic of the Faculty of Veterinary Medicine, in Cluj-Napoca, on 1 healthy pig, in november 2013. After the pig was humanely euthanized, a segment of proximal jejunum was obtained following a middle incision. All mesenteric tissues, mucosa and serosa tunica were removed from the intestin with a scalpel and moistened gauze. The material was rinsed in sterile normal saline and stored in neomycin sulfate 10 % at 4 ˚ C. Until 10 days from sampling SIS can be used with success in the surgical procedures of corneal reconstruction.

Metabolic pathways in the mixed segment of the wood-feeding termite Nasutitermes takasagoensis (Blattodea (Isoptera): Termitidae)

Alimentary canals of higher termites are equipped with a complex structural segment consisting of mesenteric and proctodeal epithelial tissues, which is termed the mixed segment. To assess metabolic functions occurring in the mixed segment, Nasutitermes takasagoensis (Shiraki) transcriptomes were obtained from the mixed segment and adjacent gut regions (midgut and first proctodeal segment) and were annotated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The predominant metabolic function detected in the mixed segment was energy production via oxidative phosphorylation. As KEGG orthologs involved in lysosomal and phagosomal systems were also characteristic of this segment, cellular components are probably recycled rather than newly produced, allowing higher energy production. The predominant adenosine triphosphate (ATP) consumer in the mixed segment was vacuolar-type H+-ATPase (V-ATPase), known to be involved in K+ transport in many insects. Based on our data, V-ATPases appear to electrogenically drive NHE6 or NHE7 (NHE6/7) K+/H+ antiporters to stimulate K+ secretion, increasing gut lumen pH. The mixed segment also expressed higher levels than did the adjacent gut regions of carbonic anhydrase, another contributor to gut alkalization through HCO3 − production. Thus, metabolic pathways in the mixed segment might promote lignocellulose solubilization in higher termites’ gut, contributing to their success.

Mast Cells‐Dependent Compromised Response of Aged Mesenteric Lymphatic Vessels and Surrounding Tissues to the Acute Inflammatory Challenge

Mesenteric lymphatic vessels (MLVs), being located at the border between the biologically aggressive environment of the gut lumen and inner compartments of the abdomen have not been studied in depth as an active component of the anti‐inflammatory defense system of the body. Aging creates several challenges for lymphatic vessels by altering their ultrastructure, contractility and consequently lymph flow as well as their microenvironment. We found an increase in number and degree of basal activation of mast cells (MC) nearby aged mesenteric lymphatic vessels. Such, as we predicted, will delimit ability of aged mesenteric tissue to respond to acute inflammatory challenge. In current study we attempted to establish mechanistic links between the aging‐associated changes in functional status of MCs and the altered responses of mesenteric tissue and MLVs to acute inflammatory insult. We used in vivo model of induction of acute peritoneal inflammation by lipopolysaccharide (LPS) treatment (24 hours after single IP injection of LPS in dose of 10 mg/kg body weight into adult (9‐mo) and aged (24‐mo) F‐344 rats). Analysis of data obtained by studies based on ruthenium red staining of MCs and by flow cytometry‐based measurements demonstrate that LPS‐induced degranulation of MCs in aged mesentery is greatly diminished. Latter co‐exists with basal activation of NF‐κB signaling in aged MLVs and mesenteric tissue therefore additional LPS‐induced NF‐κB activation is also reduced. Furthermore both mast cell stabilization by Cromolyn, or application of mixture of Histamine H1–H4 receptor blockers, are able to prevent the NF‐κB activation in mesentery/MLVs. NF‐κB, as hallmark of aging‐associated low‐grade inflammation, controls the release of pro‐inflammatory cytokines. To identify the corresponding aging‐associated differences, 24 hours after LPS injection we compared blood and mesenteric tissue (including MLVs) samples from adult and aged rats for 27 major pro‐inflammatory cytokines, using a Multiplex cytokine assay system (kit RECMAG65K27PMX, Millipore, US). The obtained results show that there is an elevation of NF‐κB‐dependent pro‐inflammatory cytokines in aged mesentery/MLVs with imbalance of Th1/Th2 cytokine profile and subsequent changes in T and B cells populations. Cumulatively, our data indicate that pre‐existing activation of MCs in aged mesentery by MLVs linked to its altered response to LPS, associated with histamine/NF‐κB‐dependent specific changes in cytokine levels. Latter can contribute to imbalance of immune cells profile and decreased ability of the aged immune system to respond to acute inflammatory challenge in peritoneal compartment of the body.Support or Funding InformationNIH/NIDDK 1R56DK099161

The Role of NADPH Oxidase Isoform 1 (NOX1) in L‐NAME‐Induced Leukocyte‐Endothelial Interactions in Rat Mesenteric Postcapillary Venules

Vascular endothelial dysfunction and subsequent inflammation underlie many pathological diseases such as cardiovascular disease, diabetes, and hypertension. Both events are principally initiated by reduced endothelial‐derived nitric oxide (NO) bioavailability and/or activation of vascular/leukocyte NADPH oxidase. NADPH oxidase has 7 isoforms (NOX1‐5 and Duox1‐2). We currently have limited knowledge regarding the roles of individual NOX isoforms in diseases, particularly NOX1, which is a major NADPH oxidase isoform in the vasculature but not in leukocytes. In this study, we evaluated the roles of NOX1 in vascular endothelial dysfunction‐induced inflammation by recording leukocyte rolling, adherence, and transmigration in a postcapillary venule of rat mesenteric tissue in real time via intravital microscopy. We superfused the mesenteric tissue with Krebs’ buffer, and Krebs’ buffer with a non‐selective NO synthase inhibitor, NG‐nitro‐L‐arginine‐methyl‐ester (L‐NAME, 50 μM) with/without a selective NOX1 inhibitor, ML171. We found that at 2 hrs of superfusion, leukocyte rolling (21±8 cells/min), adherence (3±2 cells/100 μm), and transmigration (2±1 cells/200 μm2) was minimal in Krebs’ control (n=8). By contrast, L‐NAME (n=6) significantly increased leukocyte rolling (74±12), adhesion (19±6), and transmigration (18±4) (all P&lt;0.05 compared to Krebs’ control). Whereas, ML171 (1 μM, n=7) prevented the L‐NAME‐induced effect on leukocyte rolling (25±5), adhesion (5±2), and transmigration (5±1). These findings suggest that NOX‐1 activation participates in L‐NAME induced inflammatory responses; whereas inhibition of NOX1 can mitigate inflammation following vascular endothelial dysfunction.Support or Funding InformationThis study was supported by Division of Research, the Center for Chronic Disorders of Aging, and Department of Bio‐Medical Sciences at Philadelphia College of Osteopathic Medicine.