Lymph node germinal centers form in the absence of follicular dendritic cell networks.
(1/1018)
Follicular dendritic cell networks are said to be pivotal to both the formation of germinal centers (GCs) and their functions in generating antigen-specific antibody affinity maturation and B cell memory. We report that lymphotoxin beta-deficient mice form GC cell clusters in the gross anatomical location expected of GCs, despite the complete absence of follicular dendritic cell networks. Furthermore, antigen-specific GC generation was at first relatively normal, but these GCs then rapidly regressed and GC-phase antibody affinity maturation was reduced. Lymphotoxin beta-deficient mice also showed substantial B cell memory in their mesenteric lymph nodes. This memory antibody response was of relatively low affinity for antigen at week 4 after challenge, but by week 10 after challenge was comparable to wild-type, indicating that affinity maturation had failed in the GC phase but developed later. (+info)
In vivo blood flow abnormalities in the transgenic knockout sickle cell mouse.
(2/1018)
The accepted importance of circulatory impairment to sickle cell anemia remains to be verified by in vivo experimentation. Intravital microscopy studies of blood flow in patients are limited to circulations that can be viewed noninvasively and are restricted from deliberate perturbations of the circulation. Further knowledge of sickle blood flow abnormalities has awaited an animal model of human sickle cell disease. We compared blood flow in the mucosal-intestinal microvessels of normal mice with that in transgenic knockout sickle cell mice that have erythrocytes containing only human hemoglobin S and that exhibit a degree of hemolytic anemia and pathological complications similar to the human disease. In sickle cell mice, in addition to seeing blood flow abnormalities such as sludging in all microvessels, we detected decreased blood flow velocity in venules of all diameters. Flow responses to hyperoxia in both normal and sickle cell mice were dramatic, but opposite: Hyperoxia promptly slowed or halted flow in normal mice but markedly enhanced flow in sickle cell mice. Intravital microscopic studies of this murine model provide important insights into sickle cell blood flow abnormalities and suggest that this model can be used to evaluate the causes of abnormal flow and new approaches to therapy of sickle cell disease. (+info)
Segmented filamentous bacteria are potent stimuli of a physiologically normal state of the murine gut mucosal immune system.
(3/1018)
Segmented filamentous bacteria (SFB) are autochthonous bacteria inhabiting the intestinal tracts of many species, including humans. We studied the effect of SFB on the mucosal immune system by monoassociating formerly germfree C3H/HeN mice with SFB. At various time points during 190 days of colonization, fragment cultures of small intestine and Peyer's patches (PP) were analyzed for total immunoglobulin A (IgA) and SFB-specific IgA production. Also, phenotypic changes indicating germinal center reactions (GCRs) and the activation of CD4(+) T cells in PP were determined by using fluorescence-activated cell sorter analyses. A second group of SFB-monoassociated mice was colonized with a gram-negative commensal, Morganella morganii, to determine if the mucosal immune system was again stimulated and to evaluate the effect of prior colonization with SFB on the ability of M. morganii to translocate to the spleen and mesenteric lymph nodes. We found that SFB stimulated GCRs in PP from day 6 after monoassociation, that GCRs only gradually waned over the entire length of colonization, that natural IgA production was increased to levels 24 to 63% of that of conventionally reared mice, and that SFB-specific IgA was produced but accounted for less than 1.4% of total IgA. Also, the proportion of CD4(+), CD45RBlow T cells, indicative of activated cells, gradually increased in the PP to the level found in conventionally reared mice. Secondary colonization with M. morganii was able to stimulate GCRs anew, leading to a specific IgA antibody response. Previous stimulation of mucosal immunity by SFB did not prevent the translocation of M. morganii in the double-colonized mice. Our findings generally indicate that SFB are one of the single most potent microbial stimuli of the gut mucosal immune system. (+info)
Convective oxygen transport and tissue oxygen consumption in Weddell seals during aerobic dives.
(4/1018)
Unlike their terrestrial counterparts, marine mammals stop breathing and reduce their convective oxygen transport while performing activities (e.g. foraging, courtship, aggressive interactions, predator avoidance and migration) that require sustained power output during submergence. Since most voluntary dives are believed to remain aerobic, the goal of this study was to examine the potential importance of the dive response in optimizing the use of blood and muscle oxygen stores during dives involving different levels of muscular exertion. To accomplish this, we designed a numerical model based on Fick's principle that integrated cardiac output (Vb), regional blood flow, convective oxygen transport (Q(O2)), muscle oxymyoglobin desaturation and regional rates of oxygen consumption (VO2). The model quantified how the optimal matching or mismatching of QO2 to VO2 affected the aerobic dive limit (ADL). We chose an adult Weddell seal Leptonycotes weddellii on which to base our model because of available data on the diving physiology and metabolism of this species. The results show that the use of blood and muscle oxygen stores must be completed at the same time to maximize the ADL for each level of VO2. This is achieved by adjusting Vb (range 19-94 % of resting levels) and muscle QO2 according to the rate of muscle oxygen consumption (VMO2). At higher values of VMO2, Vb and muscle perfusion must increase to maintain an appropriate QO2/VO2 ratio so that available blood and muscle oxygen stores are depleted at the same time. Although the dive response does not sequester blood oxygen exclusively for brain and heart metabolism during aerobic dives, as it does during forced submersion, a reduction in Vb and muscle perfusion below resting levels is necessary to maximize the ADL over the range of diving VO2 (approximately 2-9 ml O2 min-1 kg-1). Despite the reduction in Vb, convective oxygen transport is adequate to maintain aerobic metabolism and normal function in the splanchnic organs, kidneys and other peripheral tissues. As a result, physiological homeostasis is maintained throughout the dive. The model shows that the cardiovascular adjustments known as the dive response enable the diving seal to balance the conflicting metabolic demands of (1) optimizing the distribution and use of blood and muscle oxygen stores to maximize the ADL over the normal range of diving VO2 and (2) ensuring that active muscle receives adequate oxygen as VMO2 increases. (+info)
The colonic mesenteric margin is most susceptible to injury in an experimental model of colonic ulceration.
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BACKGROUND: Crohn's disease ileal ulcers and indomethacin-induced jejunal ulceration in the rat tend to occur in the mucosa nearest to the mesentery (mesenteric margin), an area of the bowel wall that has a critical blood supply. Mercuric chloride induces caecal and colonic ulceration in the Brown Norway rat. AIM: To examine whether the mesenteric margin is more sensitive to injury by a substance known to be vasculotoxic in the caecum and colon. METHODS: Brown Norway rats received a single subcutaneous dose of either mercuric chloride 1 mg/kg or saline. The gastrointestinal tract was examined macro- and microscopically for lesions 48 h later. The vascular anatomy of the normal rat colon and caecum was also examined using the carbon ink perfusion technique. RESULTS: Mercuric chloride induced caecal and colonic ulceration preferentially along the mesenteric margin of the bowel wall. Histologically, the lesions showed mucosal necrosis and neutrophil infiltration. There was also extensive vascular degeneration/necrosis with microaneurysm formation and extensive submucosal haemorrhage. Cellular infiltration of the vasculature was not a feature. The caecal and colonic mesenteric margins in control rats were supplied by small end arteries. CONCLUSIONS: The colonic and caecal mesenteric margins are susceptible to injury by mercuric chloride, a chemical known to induce haemorrhagic vasculopathy in the rat gastrointestinal tract. The large bowel mesenteric margin may be susceptible to injury by mercuric chloride because of the critical blood supply to that side of the bowel wall. (+info)
Differential induction of adhesion molecule and chemokine expression by LTalpha3 and LTalphabeta in inflammation elucidates potential mechanisms of mesenteric and peripheral lymph node development.
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Lymphotoxin (LT) is a member of the proinflammatory TNF family of cytokines that plays a critical role in the development of lymphoid tissue. It has previously been reported that the presence of the LTalpha transgene under the control of the rat insulin promoter results in inflammation at the sites of transgene expression. LTalpha transgene expression results in expression of the adhesion molecules VCAM, ICAM, peripheral node addressin (a marker of peripheral lymph nodes), and mucosal addressin cellular adhesion molecule (a marker of mucosal lymphoid tissue, including mesenteric lymph nodes). In this study to determine the mechanisms by which LT promotes inflammation and lymphoid tissue organization, we analyzed the regulation of expression of adhesion molecules and chemokines in LT transgenic mice. The results demonstrate that LTalpha3 induces expression of the adhesion molecules VCAM, ICAM, and mucosal addressin cellular adhesion molecule as well as the chemokines RANTES, IFN-inducible protein-10, and monocyte chemotactic protein-1, while LTalphabeta is required for the induction of peripheral node addressin that may contribute to the recruitment of L-selectinhigh CD44low naive T cells. These data provide candidate mediators of LT-induced inflammation as well as potential mechanisms by which LTalpha and LTalphabeta may differentially promote the development of mesenteric and peripheral lymph nodes. (+info)
Transmesenteric hernia after laparoscopic-assisted sigmoid colectomy.
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BACKGROUND AND OBJECTIVES: Laparoscopic-assisted surgery has been applied for a variety of colonic surgery. The objective of this paper is to demonstrate a possible and avoidable complication of laparoscopic colonic surgery. CASE PRESENTATION: A 47-year-old woman underwent gasless laparoscopic-assisted sigmoid colectomy. On the 20th postoperative day, she developed bowel obstruction. Decompression with a long tube failed to resolve the bowel obstruction. Open laparotomy was performed. Abdominal exploration revealed a loop of the small bowel incarcerated in the mesenteric defect caused by the previous operation. Adhesiolysis was performed, and the postoperative course was uneventful. DISCUSSION: Despite technical difficulty, complete closure of the mesentery after bowel resection is strongly recommended for prevention of transmesenteric incarcerated hernia after laparoscopic surgery. (+info)
Vascular endothelial growth factor attenuates leukocyte-endothelium interaction during acute endothelial dysfunction: essential role of endothelium-derived nitric oxide.
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Vascular endothelial growth factor (VEGF) is an endothelium-specific secreted protein that induces vasodilation and increases endothelial release of nitric oxide (NO). NO is also reported to modulate leukocyte-endothelium interaction. Therefore, we hypothesized that VEGF might inhibit leukocyte-endothelium interaction via increased release of NO from the vascular endothelium. We used intravital microscopy of the rat mesenteric microcirculation to measure leukocyte-endothelium interactions 2, 4, and 24 h after systemic administration of VEGF to the rat (120 microg/kg, i.v., bolus). Superfusion of the rat mesentery with either 0.5 U/ml thrombin or 50 microM L-NAME consistently increased the number of rolling, adhering, and transmigrated leukocytes (P<0.01 vs. control mesenteries superfused with Krebs-Henseleit buffer). At 4 and 24 h posttreatment, VEGF significantly attenuated thrombin-induced and L-NAME-induced leukocyte rolling, adherence, and transmigration in rat mesenteric venules. In addition, adherence of isolated rat PMNs to thrombin-stimulated mesenteric artery segments in vitro was significantly reduced in mesenteric arteries isolated from VEGF-treated rats (P<0.001 vs. control rats). Direct measurement of NO demonstrated a threefold increase in basal NO release from aortic tissue of rats injected with VEGF, at 4 and 24 h posttreatment (P<0. 01 vs. aortic tissue from control rats). Finally, systemic administration of VEGF to ecNOS-deficient mice failed to inhibit leukocyte-endothelium interactions observed in peri-intestinal venules. We concluded that VEGF is a potent inhibitor of leukocyte-endothelium interaction, and this effect is specifically correlated to augmentation of NO release from the vascular endothelium.--Scalia, R., Booth, G., Lefer, D. J. Vascular endothelial growth factor attenuates leukocyte-endothelium interaction during acute endothelial dysfunction: essential role of endothelium-derived nitric oxide. (+info)