Tissue-resident macrophages require specific milieus for the maintenance of defining gene-expression programs. Expression of the transcription factor GATA6 is required for the homeostasis, function ...and localization of peritoneal cavity-resident macrophages. Gata6 expression is maintained in a non-cell autonomous manner and is elicited by the vitamin A metabolite, retinoic acid. Here, we found that the GATA6 transcriptional program is a common feature of macrophages residing in all visceral body cavities. Retinoic acid-dependent and -independent hallmark genes of GATA6+ macrophages were induced by mesothelial and fibroblastic stromal cells that express the transcription factor Wilms’ Tumor 1 (WT1), which drives the expression of two rate-limiting enzymes in retinol metabolism. Depletion of Wt1+ stromal cells reduced the frequency of GATA6+ macrophages in the peritoneal, pleural and pericardial cavities. Thus, Wt1+ mesothelial and fibroblastic stromal cells constitute essential niche components supporting the tissue-specifying transcriptional landscape and homeostasis of cavity-resident macrophages.
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•Large cavity macrophages (LCMs) reside in peritoneal, pleural, and pericardial spaces•LCMs express the retinoic-acid-responsive transcription factor GATA6•Wt1+ stromal cells generate retinoic acid and maintain LCM GATA6 expression•Genetic ablation of Wt1+ stroma elicits loss of LCM across cavity spaces
Buechler et al. show that large cavity macrophages (LCMs), which rely on the retinoic-acid-responsive transcription factor GATA6, are found in all visceral cavity spaces. Wt1+ mesothelial and fibroblastic stromal cells maintain the LCM transcriptome in part via the generation of retinoic acid and are required for LCM homeostasis in vivo.
Inflammation generally leads to recruitment of monocyte-derived macrophages. What regulates the fate of these cells and to what extent they can assume the identity and function of resident ...macrophages is unclear. Here, we show that macrophages elicited into the peritoneal cavity during mild inflammation persist long-term but are retained in an immature transitory state of differentiation due to the presence of enduring resident macrophages. By contrast, severe inflammation results in ablation of resident macrophages and a protracted phase wherein the cavity is incapable of sustaining a resident phenotype, yet ultimately elicited cells acquire a mature resident identity. These macrophages also have transcriptionally and functionally divergent features that result from inflammation-driven alterations to the peritoneal cavity micro-environment and, to a lesser extent, effects of origin and time-of-residency. Hence, rather than being predetermined, the fate of inflammation-elicited peritoneal macrophages seems to be regulated by the environment.
The intraperitoneal route is favored for administration of inactivated and attenuated vaccines in Atlantic salmon. Nevertheless, the immune responses in the teleost peritoneal cavity (PerC) are still ...incompletely defined. In this study, we investigated the B cell responses after intraperitoneal Piscirickettsia salmonis (P. salmonis) challenge of Atlantic salmon, focusing on the local PerC response versus responses in the lymphatic organs: spleen and head kidney. We observed a major increase of leukocytes, total IgM antibody secreting cells (ASC), and P. salmonis-specific ASC in the PerC at 3- and 6-weeks post infection (wpi). The increase in ASC frequency was more prominent in the spleen and PerC compared to the head kidney during the observed 6 wpi. The serum antibody response included P. salmonis-specific antibodies and non-specific antibodies recognizing the non-related bacterial pathogen Yersinia ruckeri and the model antigen TNP-KLH. Finally, we present evidence that supports a putative role for the adipose tissue in the PerC immune response.
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•We developed P. salmonis &Y. ruckeri specific ELISpots and corresponding ELISAs.•Antibody secreting cells are mainly present in the peritoneal cavity for 6 weeks.•Immune cell marker expression suggests an immune role for the adipose tissue.
Lesser sac fluid after blunt trauma Ambinder, David; Kochuba, Matthew; Scalea, Thomas
The journal of trauma and acute care surgery,
12/2021, Letnik:
91, Številka:
6
Journal Article
The liver is positioned at the interface between two routes traversed by pathogens in disseminating infection. Whereas blood-borne pathogens are efficiently cleared in hepatic sinusoids by Kupffer ...cells (KCs), it is unknown how the liver prevents dissemination of peritoneal pathogens accessing its outer membrane. We report here that the hepatic capsule harbors a contiguous cellular network of liver-resident macrophages phenotypically distinct from KCs. These liver capsular macrophages (LCMs) were replenished in the steady state from blood monocytes, unlike KCs that are embryonically derived and self-renewing. LCM numbers increased after weaning in a microbiota-dependent process. LCMs sensed peritoneal bacteria and promoted neutrophil recruitment to the capsule, and their specific ablation resulted in decreased neutrophil recruitment and increased intrahepatic bacterial burden. Thus, the liver contains two separate and non-overlapping niches occupied by distinct resident macrophage populations mediating immunosurveillance at these two pathogen entry points to the liver.
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•A distinct subset of resident macrophages (LCMs) occupies the hepatic capsule•LCMs are replenished from blood monocytes in the steady state•LCMs recruit neutrophils in response to bacteria reaching the liver capsule•LCM depletion decreases neutrophil recruitment and increases liver pathogen load
The hepatic sinusoids harbor a well-characterized resident macrophage population, Kupffer cells. Sierro et al. report an additional liver-resident macrophage population occupying the hepatic capsule, phenotypically and developmentally distinct from Kupffer cells, which plays a role in immunosurveillance by sensing peritoneal pathogens and recruiting neutrophils to control intrahepatic bacterial dissemination.
B-1 cells are fetal-origin B lymphocytes with unique developmental and functional characteristics that can generate natural, polyreactive antibodies with important functions in tissue homeostasis and ...immune defense. While B-1 cell frequencies in bone marrow and secondary lymphoid tissues are low, relative high frequencies exist within peritoneal and pleural cavities of mice, including both CD5
and CD5
B-1 cells. These cells represent B-1 reservoirs that, when activated, migrate to lymphoid tissues to secrete antibodies and/or cytokines. Here, we outline efficient methods for the extraction and magnetic isolation of CD5
B-1 cells from the peritoneal and pleural cavities as well as the separation and phenotypic characterization of CD5
and CD5
B-1 cells by flow cytometry.
Macrophages are intimately involved in the pathophysiology of endometriosis, a chronic inflammatory disorder characterized by the growth of endometrial-like tissue (lesions) outside the uterus. By ...combining genetic and pharmacological monocyte and macrophage depletion strategies we determined the ontogeny and function of macrophages in a mouse model of induced endometriosis. We demonstrate that lesion-resident macrophages are derived from eutopic endometrial tissue, infiltrating large peritoneal macrophages (LpM) and monocytes. Furthermore, we found endometriosis to trigger continuous recruitment of monocytes and expansion of CCR2+ LpM. Depletion of eutopic endometrial macrophages results in smaller endometriosis lesions, whereas constitutive inhibition of monocyte recruitment significantly reduces peritoneal macrophage populations and increases the number of lesions. Reprogramming the ontogeny of peritoneal macrophages such that embryo-derived LpM are replaced by monocyte-derived LpM decreases the number of lesions that develop. We propose a putative model whereby endometrial macrophages are "proendometriosis" while newly recruited monocyte-derived macrophages, possibly in LpM form, are "antiendometriosis." These observations highlight the importance of monocyte-derived macrophages in limiting disease progression.
Uterine fibroids, which are common benign tumors, rarely cause acute complications. We herein report a case of hemoperitoneum associated with uterine fibroid that could be diagnosed preoperatively ...with contrast-enhanced computerized tomography (CT).
A 48-year-old woman with uterine fibroid developed extremely severe lower abdominal pain on the first day of her menstrual period.
Ultrasonography and contrast-enhanced CT revealed a uterine fibroid and extravasation from the dilated vessels of the uterine fibroid.
Emergent abdominal hysterectomy was performed.
The total amount of bleeding was 4,600 mL. Intraoperative blood salvage (1,357 mL), 6 units of red blood cells, 4 units of fresh frozen plasma, and 20 units of platelet concentrates were transfused. The postoperative course was uneventful. Pathological examination confirmed a benign uterine fibroid.
CT could be useful to determine a diagnosis for bleeding from ruptured subserosal uterine fibroid.
Peritoneal tissue-resident macrophages have broad functions in the maintenance of homeostasis and are involved in pathologies within local and neighboring tissues. Their functions are dictated by ...microenvironmental cues; thus, it is essential to investigate their behavior in an in vivo physiological niche. Currently, specific peritoneal macrophage-targeting methodologies employ whole-mouse transgenic models. Here, a protocol for effective in vivo modulation of mRNA and small RNA species (e.g., microRNA) expression in peritoneal macrophages using lentivirus particles is described. Lentivirus preparations were made in HEK293T cells and purified on a single sucrose layer. In vivo validation of lentivirus effectivity following intraperitoneal injection revealed predominant infection of macrophages restricted to local tissue. Targeting of peritoneal macrophages was successful during homeostasis and thioglycolate-induced peritonitis. The limitations of the protocol, including low-level inflammation induced by intraperitoneal delivery of lentivirus and time restrictions for potential experiments, are discussed. Overall, this study presents a quick and accessible protocol for the rapid assessment of gene function in peritoneal macrophages in vivo.
Desmoplastic small round-cell tumour is a very rare neoplasm, which usually arises from the abdominal or pelvic peritoneum of adolescents and young adults. Early diagnosis is difficult, because most ...tumours present with non-specific gastrointestinal symptoms after a long asymptomatic period. It is generally a very aggressive tumour, which grows rapidly with poor prognosis and an overall five-year survival rate of 15% despite multimodal treatment. Despite multiple treatment strategies, the management of desmoplastic small round-cell tumour still remains a clinical challenge and no consensus about a therapeutic protocol has been established. A 35-year-old man presented with mild abdominal pain, constipation and weight gain, and was eventually diagnosed with desmoplastic small round-cell tumour, which was shown to be limited to the abdomen. After incomplete debulking surgery, radiotherapy and chemotherapy, he developed multiple metastatic nodular foci in chest and the pleura and, unfortunately, he died due to disease progression.