IL-1ß Impacts Vascular Integrity and Lymphatic Function in the Embryonic Omentum.

BACKGROUND: The chromatin-remodeling enzyme BRG1 (brahma-related gene 1) regulates gene expression in a variety of rapidly differentiating cells during embryonic development. However, the critical genes that BRG1 regulates during lymphatic vascular development are unknown. METHODS: We used genetic and imaging techniques to define the role of BRG1 in murine embryonic lymphatic development, although this approach inadvertently expanded our study to multiple interacting cell types. RESULTS: We found that omental macrophages fine-tune an unexpected developmental process by which erythrocytes escaping from naturally discontinuous omental blood vessels are collected by nearby lymphatic vessels. Our data indicate that circulating fibrin(ogen) leaking from gaps in omental blood vessels can trigger inflammasome-mediated IL-1ß (interleukin-1ß) production and secretion from nearby macrophages. IL-1ß destabilizes adherens junctions in omental blood and lymphatic vessels, contributing to both extravasation of erythrocytes and their uptake by lymphatics. BRG1 regulates IL-1ß production in omental macrophages by transcriptionally suppressing the inflammasome trigger RIPK3 (receptor interacting protein kinase 3). CONCLUSIONS: Genetic deletion of Brg1 in embryonic macrophages leads to excessive IL-1ß production, erythrocyte leakage from blood vessels, and blood-filled lymphatics in the developing omentum. Altogether, these results highlight a novel context for epigenetically regulated crosstalk between macrophages, blood vessels, and lymphatics.

Abnormal Intestinal Anatomy in Late-stage Human Fetuses: Three Case Series.

OBJECTIVE: We reported three cases of fetuses with abnormal intestinal anatomy found during our recent study of the transverse mesocolon using 20 late-stage fetuses. CASES: The first case (CRL: 328 mm) appeared to have a duodenum and transverse colon trapped in Winslow's foramen (foramen epiploicum) and the duodenum superior portion elongated rightward. The second case (CRL: 264 mm) had a transverse colon inserted deeply into a space between the right kidney and duodenum. The third case (CRL: 276 mm) had a descending colon that ran inferiorly through a deep space between the left kidney and duodenum. Each case had a greater omentum that was shifted leftward, but this is usual. These 3 abnormalities were not evident in the anterior view during dissection of the liver, stomach, jejunum, and ileum. With underdeveloped pancreatic ducts due to unknown reason other than the internal hernia, the first case seemed to be fatal after birth. However, the second and third cases could have recovered after birth because there was no evidence of definite malrotation and because of loose attachments of the intestines to surrounding structures. CONCLUSIONS: The intestinal morphologies described here could cause some sort of symptoms, such as abdominal pain, whose cause might be difficult to determine.

Accessory Spleen in the Greater Omentum: Embryology and Revisited Prevalence Rates.

PURPOSE: To investigate in a large sample the prevalence rates of accessory spleens located in the greater omentum and to explain the embryological background and the vascular supply of this rare congenital disorder. METHODS: Evaluation of the presence of accessory spleens located in the greater omentum was performed in 5 different international anatomical centers investigating a total of 1,045 body donors. Arterial and venous blood supply and the precise location of the respective vasculature within the splenic ligaments are described based on dissection of this rare condition in a male specimen. RESULTS: The reported prevalence rates from 5 different centers were: 0.5% (out of 380 body donors), 0% (out of 230 donors), 0% (out of 200 donors), 2% (out of 200 donors), and 0% (out of 35 donors). The cumulative prevalence rate obtained from 1,045 anatomical dissections was 0.6%. The identified accessory spleen measured 3 × 3 × 2.5 cm and was located in the left upper abdominal quadrant. A vascular stag 7.5 cm in length was identified within the gastro-splenic ligament, containing an artery and a vein piercing the greater omentum from posterior. CONCLUSION: An accessory spleen located in the greater omentum is a rare congenital disorder. Physicians should be aware of the fact that in patients without any representative symptom history a nodular mass located within the greater omentum could be an accessory spleen.

Topographical anatomy of Spiegel's lobe and its adjacent organs in mid-term fetuses: Its implication on the development of the lesser sac and adult morphology of the upper abdomen.

At 8-16 weeks of gestation, Spiegel's lobe of the caudate lobe appears as a sac-like herniation of the liver parenchyma between the inferior vena cava and ductus venosus or Arantius' duct. In 5 of 11 fetuses at 20-30 weeks of gestation, we found that an external notch was formed into the posterior aspect of the caudate lobe by a peritoneal fold containing the left gastric artery. This notch appeared to correspond to that observed in adults, which is usually seen at the antero-inferior margin of the lobe after rotation of the lobe along the horizontal or transverse axis. However, the notch did not accompany two of the three fetuses in which the left hepatic artery originated from the left gastric artery. Notably, until 9-10 weeks of gestation, the inferior and left part of Spiegel's lobe rode over the hepatoduodenal ligament and protruded medially into the lesser sac (bursa omentalis) behind the stomach. Thus, the fetal Winslow's foramen was located at the "superior" side of the ligament. However, as seen in adults, the protruding Spiegel's lobe was located at the posterior side of the lesser omentum. Therefore, a hypothetical rotation along the transverse axis in the later stages of development seems necessary to explain this repositioning. Considering that Spiegel's lobe develops faster than surrounding structures, it is likely that the lesser sac resulting from the rotation of the gastrointestinal tract, which actively contributes to facilitate the growth of the Spiegel lobe.

The greater omentum. Anatomy, embryology, and surgical applications.

The significance of the greater omentum has been discovered recently by surgeons of various disciplines because it provides an excellent plastic material against inflammation and irradiation and for repair of defects that can be applied in the abdominal cavity; or it can be exteriorized and lengthened at a vascular pedicle and detached using microvascular anastomoses. Anatomic features, such as the volume of the omentum and the arrangement of the blood vessels, determine the lines of dissection. The eminent omental potential and the different biochemical and immunologic functions are unique, and can be related to specific anatomic structures, some of which may be drawn back to its embryologic sources. The ability of absorption and adhesion formation, neovascularization, and infection defense by the omentum protects against irradiation damage, accelerates healing of dead space, and improves the complication rate and quality of life after application to a wound bed.

Stem cell emergence and hemopoietic activity are incompatible in mouse intraembryonic sites.

In the mouse embryo, the generation of candidate progenitors for long-lasting hemopoiesis has been reported in the paraaortic splanchnopleura (P-Sp)/ aorta-gonad-mesonephros (AGM) region. Here, we address the following question: can the P-Sp/AGM environment support hemopoietic differentiation as well as generate stem cells, and, conversely, are other sites where hemopoietic differentiation occurs capable of generating stem cells? Although P-Sp/AGM generates de novo hemopoietic stem cells between 9.5 and 12.5 days post coitus (dpc), we show here that it does not support hemopoietic differentiation. Among mesoderm-derived sites, spleen and omentum were shown to be colonized by exogenous cells in the same fashion as the fetal liver. Cells colonizing the spleen were multipotent and pursued their evolution to committed progenitors in this organ. In contrast, the omentum, which was colonized by lymphoid-committed progenitors that did not expand, cannot be considered as a hemopoietic organ. From these data, stem cell generation appears incompatible with hemopoietic activity. At the peak of hemopoietic progenitor production in the P-Sp/AGM, between 10.5 and 11.5 dpc, multipotent cells were found at the exceptional frequency of 1 out of 12 total cells and 1 out of 4 AA4.1+ cells. Thus, progenitors within this region constitute a pool of undifferentiated hemopoietic cells readily accessible for characterization.

Ontogeny of milky spots in the human greater omentum: an immunochemical study.

BACKGROUND: Milky spots in the human greater omentum are preformed specific accumulations of primarily macrophages within the stroma of the greater omentum. To obtain a better understanding of milky spots in the human greater omentum, the development and the earliest forms of milky spots in the human greater omentum were studied, with special attention to the macrophage population. METHODS: Specimens of human greater omentum were obtained from fetuses of 20 to 40 weeks gestation and one newborn three days old (n = 6). Using mature macrophages (RFD 7), activated macrophages (RFD 1), B-lymphocytes (CD 22), and T-lymphocytes (CD 2), and immunoperoxydase labeling, the percentage of these cells in developing milky spots and the development of milky spots were studied by light microscopy. A time-dependent increase in the percentage of positive staining cells and the size of clusters was analyzed using the non-parametric Spearman rank correlation test. RESULTS: Small accumulations of cells with about 50% monocytes/macrophages were present at 20 weeks of gestation. With increasing gestational age the number of clusters of cells increased significantly (P < 0.01) as well as their size (P < 0.01). Starting at 29 weeks, vascularized clusters of cells were seen; true milky spots were present at 35 weeks. A significant (P < 0.05) increase in the percentage of mature macrophages was found in developing milky spots, whereas no activated macrophages were seen. The percentage of B-lymphocytes and T-lymphocytes found in the clusters of cells and milky spots increased significantly (P < 0.05) but did not exceed 10% of the total number of cells. CONCLUSIONS: From our data it can be concluded that milky spots are specific structures in the greater omentum formed between the 20th and 35th week of gestation. Further, we concluded that immature cells (promonocytes) mature locally in developing milky spots.

[The loop-like growth of the vessels and the embryonic morphogenesis of the human intraorganic circulatory system]. / Petlevidnyi rost sosudov i émbrional'nyi morfogenez vnutriorgannoi sistemy krovoobrashcheniia cheloveka.

Development of the vascular bed during embryogenesis in man occurs through loop-like growth of vessels appearing as multiplication, integration, and morphofunctional transformation of vessel loops. Growth of loops provides for the establishment of transport vessels in organs and tissues, and loop integration leads to the establishment of microcirculation with the appearance of connecting and major capillaries, from which true capillaries and capillary networks are formed. Precapillary arterioles and postcapillary venules can be identified topographically in the capillary networks. Formation of blood microcirculation system is complete when morphofunctional arrangement of integrated and nonintegrated loops takes place with the appearance of arterioles and venule collaterals and arterio-venule anastomoses in the vascular network.

Ontogeny of milky spots in the fetal lamb omentum.

Milky spots in the fetal lamb omentum were observed by light and electron microscopy under normal conditions and after intraperitoneal carbon injection in utero. Rudimentary milky spots first appeared as small aggregations of cells along capillaries of the omental branch of the right ruminal artery at 72 days of gestation. At 116 days of gestation, macrophages were detected immunohistochemically in the milky spots. At 125 days of gestation, T cells were detected in the milky spots, but B cells were absent. Under the conditions induced by intraperitoneal injection of carbon suspension, openings were observed between the omental mesothelial cells, and macrophage aggregations appeared on the surface of the omentum through the openings. At 148 days of gestation (newborn), the milky spots were noted as black spots because of aggregation of carbon laden macrophages. The present study demonstrates that milky spots are present at fixed sites in the fetal lamb omentum by the middle of the term, and that at birth the macrophages on the spots already possess phagocytotic ability. The fetus develops the ability to protect the peritoneal cavity by producing peritoneal macrophages from the milky spots in the greater omentum even in utero.

[The morphogenesis of the microcirculatory bed in ontogeny and the pathology of its development in the early postnatal period in congenital heart defects]. / Morfogenez mikrogemotsirkuliatornogo rusla v ontogeneze i patologiia ego razvitiia v rannem postnatal'nom periode pri vrozhdennykh porokakh serdtsa.

Circulation system of the omentum majus is studied in human fetuses (42) and children up to 3 years of age (108 with a premature delivery and 73 delivered normally). Pathologic alterations in the microcirculatory system are shown to result, during an early postnatal period, from hypovolemia of the greater circulation and tissue ischemia.

Restricted kappa chain expression in early ontogeny: biased utilization of V kappa exons and preferential V kappa-J kappa recombinations.

To determine the extent of kappa chain diversity in the preimmune repertoire early in development, kappa cDNA libraries were analyzed from 15-d old fetal omentum, 18-d-old fetal liver, and 3-wk old bone marrow. An anchored polymerase chain reaction approach was used to avoid bias for particular V kappa families. From the sequence analysis of 27 bone marrow clones, 10 different families and 20 unique V kappa genes were identified. In contrast, the V kappa expression in the fetus is highly restricted and clearly differs from the broader distribution see in 3-wk-old bone marrow. Although several V kappa families were represented in the fetal library including V kappa 9, V kappa 10, V kappa 4,5, V kappa 8, and V kappa 1, one or two members of individual families were observed repeatedly. The fetal liver and omentum libraries were found to be largely overlapping. Given the V kappa families/exons identified in the fetal sequences, the mechanism of kappa rearrangements in the early repertoire appears to occur predominantly by inversion. Importantly, the fetal repertoire was further restricted by dominant V kappa-J kappa combinations such as V kappa 4,5-J kappa 5, V kappa 9-J kappa 4, and V kappa 10-J kappa 1. Since in some cases independent rearrangements could be established, the results indicate a bias for particular V kappa-J kappa joins. The results also suggest that clonal expansion/selection in the fetal repertoire takes place after light chain rearrangement as opposed to at the pre-B cell level in the bone marrow. The restriction observed in kappa light chain expression together with known restrictions in gene usage and junctional diversity at the heavy chain level indicate a remarkably conserved fetal repertoire.

The fetal omentum in mice and humans. A site enriched for precursors of CD5 B cells early in development.

From these studies the fetal omentum appears to be an important site of B-cell generation in humans and a source of CD5 B cells in mice. We have analyzed the fetal omentum in other species and have found that B-cell development as determined by the presence of cytoplasmic IgM+ pre-B cells is also detected in the fetal rabbit omentum. We do not know if there is bias towards the production of CD5 B cells in this species; however, these preliminary results demonstrate that this site may be conserved throughout evolution in mammals as a site of B-cell generation. Because the fetal liver is also a source of precursors that can reconstitute this B-cell subset, what is the relationship between omentum and liver during the development of Ly-1 B cells? The most obvious relationship between these two sites is that cells simply migrate from one location to the other; that is, precursor cells may migrate from the fetal liver into the fetal omentum and in this milieu give rise to exclusively Ly-1+ B cells or the sister population. Alternatively, precursors of Ly-1 B cells may arise in the omentum and migrate to the liver. This is demonstrated graphically in the diagram (Fig. 6a) of a transverse section through an 8-week human fetus. In this paper, however, we suggest a model for the development of Ly-1+ B cells from the omentum and liver in which Ly-1 B cells arise from distinct precursors located in situ in the mesodermally derived omentum and mesothelial-derived liver capsule. The omentum primordia forms as the back to back fusion of the mesodermally derived lining of the peritoneal cavity, and this lining surrounds the developing gut when the liver begins to develop as an outgrowth of the intestinal primordia at approximately 3.5 weeks gestation; the outer covering or capsule of the liver is derived from the same tissue of origin as the omentum. Figure 6B is a diagram of a section through the same plane as Figure 6A but the body wall has been omitted. We propose that the Ly-1+ B cells arise in situ in the omentum and lining of the liver as indicated in Figure 6B. That Ly-1+ B cells arise from distinct precursors has been suggested by others, but ours is the first evidence for a developmental site that apparently contains B-cell progenitors for this B-cell subset.

The human fetal omentum: a site of B cell generation.

The fetal mouse omentum has been shown to be a source of precursors that exclusively reconstitutes Ly1+ B cells and the closely related Ly1- sister population, but not conventional B cells or T cells. We have extended these studies to compare B cell development in the human fetal omentum, liver, and spleen, and to demonstrate that the pro/pre-B cell compartment (CD24+, sIgM-) is detected in the omentum and liver but not spleen as early as 8 wk of gestation. From 8 to 12 wk of gestation, the proportions of IgM+ cells that were pre-B cells (cIgM+/sIgM-) in the omentum and liver were 53 +/- 15% and 45 +/- 13%, respectively, and IgM+ cells were not detectable in the spleen. After 12 wk, the percentage of pre-B cells was unchanged in the fetal liver (41 +/- 10%) but decreased significantly in the omentum (25 +/- 14%); pre-B cells were now detected in the spleen but at much lower percentages (2 +/- 3%) than either the omentum or liver. The nuclear enzyme, Tdt, was detected in approximately 25% of the CD24+ cells in the omentum and liver during the 8-12-wk time period, however, Tdt+ cells were not detected in the spleen. Approximately 40% of the mature B cells found in the omentum and spleen were CD5+ compared with only 20% in the liver. These results demonstrate that the fetal omentum, like the fetal liver and bone marrow, is a primary site of B cell development.

Infarto segmentario primario e idiopático de epiplon mayor causa poco frecuente de abdomen agudo / Primary idiopathic segmental infarction of the greater omentum, uncommon cause of acute abdominal pain

Se informan 5 casos de infarto segmentario e idiopático de epiplón mayor, atendidos entre 1987 y 1989. Se trata de una causa infrecuente de abdomen agudo, caracterizada por dolor en el hemiabdomen derecho que simula apendicitis o colecistitis aguda. El diagnóstico preoperatorio correcto muy raramente es considerado. El tratamiento quirúrgico con exéresis de la zona infartada resuelve la dolencia sin evidencia de recidiva. Se analiza la probable etiología de origen embriológico que mejor explica el infarto epiploico y su zona de ocurrencia

[Ansiform growth of blood vessels as a fundamental principle of angiogenesis]. / Petlevidnyi rost sosudov kak osnovopolagaiushchii printsip vaskulogeneza.

Succession in formation of blood bed of the greater omentum has been studied in human fetuses (42), in premature children with the body mass of 900-2,500 g (108) and in mature children up to 3 years of age (48). Vasculogenesis in the organ of 12-week-old fetuses and in older ones is demonstrated as an ansiform growth of the vessels. In the vascular loop the afferent geniculum contains differential signs of the arterial, and the different one--the venous part of the blood bed. The top of the loop contains a growth bud and is a zone of growth; it ensures proliferation of the vascular loops and their spreading in the growing tissue mass in the organ. This principle of growth provides a ramified system of arteries and veins, reiterating the course and branching of each other. Against the background of the ansiform growth of the vessels capillary formation begins, at first connective, and then true capillaries are formed. Basing on the data obtained a conception of vasculogenesis in ontogenesis is formulated. Its main stages are--period of ansiform growth of the vessels and period of capillary formation. In the latter should be distinguished appearance of connective capillaries and formation of truely capillary network.

[Main principles of the organization of the microcirculatory bed of the human greater omentum in early ontogenesis]. / Osnovnye printsipy organizatsii gemomikrotsirkuliatornogo rusla bol'shogo sal'nika cheloveka v rannem ontogeneze.

The formation process of the terminal blood bed of the greater omentum has been studied in 42 human fetuses 14--28-week-old. The main peculiarities of the greater omentum blood bed by the 14th week of development are: paired arrangement of the afferent and deferent blood vessels and loop-shaped type of capillary growth, that joining the arteriole and venule, lend the blood stream a maximally centralized character. In 15--16 weeks of the fetal development in the omentum another type of the vascular growth occurs, characterized with appearance of single angioblastic processes that branch off the apex of the capillary loops. As a result new capillaries form; they connect apices of the capillary loops, that in their turn make bases for developing a true capillary network. Together with this, presence in ontogenesis of an autochthonous way of capillary appearance is proved, their connection with the closed blood stream is followed. Distinguishing of the loop-shaped stage in the capillary growth determines certain difference between vasculogenesis in ontogenesis and the vascular growth at reparative regeneration, since the base for the latter is only the capillary growth by means of single angioblastic processes.

[Spatial organization of the lesser peritoneal sac during the early stages of human ontogeny]. / Prostranstvennaia organizatsiia malogo peritoneal'nogo meshka na rannikh étapakh ontogeneza cheloveka.

In 63 series of histological sections of human embryos and prefetuses (4-13 weeks) and in 30 corpses of fetuses and stillborns it has been stated that during the 4th week certain changes occur resulting in formation of the lesser peritoneal sac. It further develops into 3 sections: vestibulum bursae omentalis, bursa omentalis proper and cavity of the omentum majus. Spatial-temporal organization of the lesser peritoneal sac is neither connected with development of separate organs or structures, nor with independent growth, but with the process of development of the whole organocomplex of the upper part of the abdominal cavity, formation of topography and organs' fixation, growth peculiarities of the dorsal mesogastrium. The bursa omentalis proper is forming at the expense of retransformation of the hepatogastric pocket, dependent on growth of the dorsal mesogastrium and on a change in the stomach position. The vestibulum bursae omentalis appears in connection with development and formation of the liver topography, lesser omentum and duodenum. The right pulmoesophagial pocket is interrupted by a developing diaphragm with formation of the superior torsion of the bursa omentalis. Disorders in fixation processes of the organs in the superior part of the abdominal cavity and formation of the bursa omentalis topography can serve as a morphological prerequisite for cysts developing in the retroperitoneal space and hernias of the foramen epiploicum.