A surgical trauma results within minutes in exudation, platelets, and fibrin deposition. Within hours, the denuded area is covered by tissue repair cells/macrophages, starting a cascade of events. ...Epithelial repair starts on day 1 and is terminated by day 3. If repair is delayed by decreased fibrinolysis, local inflammation, or factors in peritoneal fluid, fibroblast growth starting on day 3 and angiogenesis starting on day 5 results in adhesion formation. For adhesion formation, quantitatively more important are factors released into the peritoneal fluid after retraction of the fragile mesothelial cells and acute inflammation of the entire peritoneal cavity. This is caused by mechanical trauma, hypoxia (e.g., CO
pneumoperitoneum), reactive oxygen species (ROS; e.g., open surgery), desiccation, or presence of blood, and this is more severe at higher temperatures. The inflammation at trauma sites is delayed by necrotic tissue, resorbable sutures, vascularization damage, and oxidative stress. Prevention of adhesion formation therefore consists of the prevention of acute inflammation in the peritoneal cavity by means of gentle tissue handling, the addition of more than 5% N
O to the CO
pneumoperitoneum, cooling the abdomen to 30°C, prevention of desiccation, a short duration of surgery, and, at the end of surgery, meticulous hemostasis, thorough lavage, application of a barrier to injury sites, and administration of dexamethasone. With this combined therapy, nearly adhesion-free surgery can be performed today. Conditioning alone results in some 85% adhesion prevention, barriers alone in 40%-50%.
Peritoneal immune cells reside unanchored within the peritoneal fluid in homeostasis. Here, we examined the mechanisms that control bacterial infection in the peritoneum using a mouse model of ...abdominal sepsis following intraperitoneal Escherichia coli infection. Whole-mount immunofluorescence and confocal microscopy of the peritoneal wall and omentum revealed that large peritoneal macrophages (LPMs) rapidly cleared bacteria and adhered to the mesothelium, forming multilayered cellular aggregates composed by sequentially recruited LPMs, B1 cells, neutrophils, and monocyte-derived cells (moCs). The formation of resident macrophage aggregates (resMφ-aggregates) required LPMs and thrombin-dependent fibrin polymerization. E. coli infection triggered LPM pyroptosis and release of inflammatory mediators. Resolution of these potentially inflammatory aggregates required LPM-mediated recruitment of moCs, which were essential for fibrinolysis-mediated resMφ-aggregate disaggregation and the prevention of peritoneal overt inflammation. Thus, resMφ-aggregates provide a physical scaffold that enables the efficient control of peritoneal infection, with implications for antimicrobial immunity in other body cavities, such as the pleural cavity or brain ventricles.
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•LPMs drive the defense against E. coli through the formation of resident macrophage aggregates•Resident macrophage aggregates are mesothelium-bound, fibrin-dependent immune cell scaffolds•During the resolution of infection, LPMs promote moC recruitment to resident macrophage aggregates•moCs control inflammation through fibrinolysis-driven resident macrophage aggregate disaggregation
Peritoneal immune cells reside unanchored within the peritoneal fluid in homeostasis. Vega-Pérez et al. reveal that large peritoneal macrophages drive the formation of mesothelium-bound, fibrin-dependent, multicellular aggregates, which enable peritoneal immune cells to control bacterial infection. Such resident macrophage aggregates may be central to antimicrobial immunity in other body cavities, such as the pleural cavity or brain ventricles.
Tissue macrophages play a crucial role in the maintenance of tissue homeostasis and also contribute to inflammatory and reparatory responses during pathogenic infection and tissue injury. The high ...heterogeneity of these macrophages is consistent with their adaptation to distinct tissue environments and specialization to develop niche-specific functions. Although peritoneal macrophages are one of the best-studied macrophage populations, recently it was demonstrated the co-existence of two subsets in mouse peritoneal cavity (PerC), which exhibit distinct phenotypes, functions, and origins. These macrophage subsets have been classified, according to their morphology, as large peritoneal macrophages (LPMs) and small peritoneal macrophages (SPMs). LPMs, the most abundant subset under steady state conditions, express high levels of F4/80 and low levels of class II molecules of the major histocompatibility complex (MHC). LPMs appear to be originated from embryogenic precursors, and their maintenance in PerC is regulated by expression of specific transcription factors and tissue-derived signals. Conversely, SPMs, a minor subset in unstimulated PerC, have a F4/80(low)MHC-II(high) phenotype and are generated from bone-marrow-derived myeloid precursors. In response to infectious or inflammatory stimuli, the cellular composition of PerC is dramatically altered, where LPMs disappear and SPMs become the prevalent population together with their precursor, the inflammatory monocyte. SPMs appear to be the major source of inflammatory mediators in PerC during infection, whereas LPMs contribute for gut-associated lymphoid tissue-independent and retinoic acid-dependent IgA production by peritoneal B-1 cells. In the previous years, considerable efforts have been made to broaden our understanding of LPM and SPM origin, transcriptional regulation, and functional profile. This review addresses these issues, focusing on the impact of tissue-derived signals and external stimulation in the complex dynamics of peritoneal macrophage populations.
The peritoneal cavity (PerC) is a unique compartment within which a variety of immune cells reside, and from which macrophages (MØ) are commonly drawn for functional studies. Here we define two MØ ...subsets that coexist in PerC in adult mice. One, provisionally called the large peritoneal MØ (LPM), contains approximately 90% of the PerC MØ in unstimulated animals but disappears rapidly from PerC following lipopolysaccharide (LPS) or thioglycolate stimulation. These cells express high levels of the canonical MØ surface markers, CD11b and F4/80. The second subset, referred to as small peritoneal MØ (SPM), expresses substantially lower levels of CD11b and F4/80 but expresses high levels of MHC-II, which is not expressed on LPM. SPM, which predominates in PerC after LPS or thioglycolate stimulation, does not derive from LPM. Instead, it derives from blood monocytes that rapidly enter the PerC after stimulation and differentiate to mature SPM within 2 to 4 d. Both subsets show clear phagocytic activity and both produce nitric oxide (NO) in response to LPS stimulation in vivo. However, their responses to LPS show key differences: in vitro, LPS stimulates LPM, but not SPM, to produce NO; in vivo, LPS stimulates both subsets to produce NO, albeit with different response patterns. These findings extend current models of MØ heterogeneity and shed new light on PerC MØ diversity, development, and function. Thus, they introduce a new context for interpreting (and reinterpreting) data from ex vivo studies with PerC MØ.
A growing body of evidence indicates that resolution of acute inflammation is an active process. Resolvins are a new family of lipid mediators enzymatically generated within resolution networks that ...possess unique and specific functions to orchestrate catabasis, the phase in which disease declines. Resolvin D2 (RvD2) was originally identified in resolving exudates, yet its individual contribution in resolution remained to be elucidated. Here, we establish RvD2's potent stereoselective actions in reducing excessive neutrophil trafficking to inflammatory loci. RvD2 decreased leukocyte-endothelial interactions in vivo by endothelial-dependent nitric oxide production, and by direct modulation of leukocyte adhesion receptor expression. In mice with microbial sepsis initiated by caecal ligation and puncture, RvD2 sharply decreased both local and systemic bacterial burden, excessive cytokine production and neutrophil recruitment, while increasing peritoneal mononuclear cells and macrophage phagocytosis. These multi-level pro-resolving actions of RvD2 translate to increased survival from sepsis induced by caecal ligation and puncture and surgery. Together, these results identify RvD2 as a potent endogenous regulator of excessive inflammatory responses that acts via multiple cellular targets to stimulate resolution and preserve immune vigilance.
Breaking the long-held paradigm that primary B cells are not phagocytic, several studies have demonstrated recently that B cells from fish, amphibians, and reptilians have a significant phagocytic ...capacity. Whether such capacity has remained conserved in certain mammalian B cell subsets is presently an enigma. Here, we report a previously unrecognized ability of PerC B-1a and B-1b lymphocytes to phagocytose latex beads and bacteria. In contrast, B-2 lymphocytes had an almost negligible ability to internalize these particles. Upon phagocytosis, B-1a and B-1b cells were able to mature their phagosomes into phagolysosomes and displayed the ability to kill internalized bacteria. Importantly, B-1a and B-1b cells effectively present antigen recovered from phagocytosed particles to CD4(+) T cells. However, these cells showed a much lower competence to present soluble antigen or antigen from large, noninternalized particles. B-1 B cells presented particulate and soluble antigen to CD4(+) T cells more efficiently than macrophages, whereas DCs were the most potent APCs. The novel phagocytic and microbicidal abilities identified in B-1 B lymphocytes strengthen the innate nature that has long been attributed to these cells. In the context of adaptive immunity, we show that these innate immune processes are relevant, as they enable B-1 B cells to present phagocytosable particulate antigen. These capacities position these cells at the crossroads that link innate with adaptive immune processes. In a broader context, these newly identified capacities of B-1 B cells further support the previously recognized functional, developmental, and evolutionary relationships between these cells and macrophages.
Background
There is lack of uniformity in the utilization of peritoneal cytology in gastric cancer management. The identification of intraperitoneal free cancer cells (IFCCs) is believed to confer ...poor prognosis. However, while some of these patients are palliated, others may undergo more aggressive therapies. In this review, we aimed to identify and synthesize findings on the use of peritoneal cytology in predicting peritoneal recurrence and overall survival in curative gastric cancer patients.
Methods
Electronic literature searches were conducted using Medline, EMBASE, and the Cochrane Central Register of Controlled Trials from January 1, 1998 to December 31, 2009. We determined the accuracy, sensitivity, and specificity of peritoneal cytology in predicting peritoneal recurrence based on four techniques—conventional cytology, immunoassay, immunohistochemistry, and reverse transcriptase-polymerase chain reaction. Recurrence rates and overall survival rates for curative patients were determined, based on positivity or negativity for IFCCs.
Results
Twenty-eight articles were included. All four techniques showed wide variations in accuracy, sensitivity, and specificity in predicting peritoneal recurrence. Recurrence rates for patients positive for IFCCs ranged from 11.1 to 100%, while those negative for IFCCs had recurrence rates of 0–51%. Overall survival was significantly reduced for patients with positive IFCCs. Short follow-up periods and possible duplication of results may limit result interpretation.
Conclusion
The presence of IFCCs appears to increase the risk of peritoneal recurrence and is associated with worse overall survival in gastric cancer patients. Further incorporation of peritoneal cytology in clinical decision-making in gastric cancer depends on the development of a consistently accurate and rapid IFCC detection method.
During injury, monocytes are recruited from the circulation to inflamed tissues and differentiate locally into mature macrophages, with prior reports showing that cavity macrophages of the peritoneum ...and pericardium invade deeply into the respective organs to promote repair. Here we report a dual recombinase-mediated genetic system designed to trace cavity macrophages in vivo by intersectional detection of two characteristic markers. Lineage tracing with this method shows accumulation of cavity macrophages during lung and liver injury on the surface of visceral organs without penetration into the parenchyma. Additional data suggest that these peritoneal or pleural cavity macrophages do not contribute to tissue repair and regeneration. Our in vivo genetic targeting approach thus provides a reliable method to identify and characterize cavity macrophages during their development and in tissue repair and regeneration, and distinguishes these cells from other lineages.
The development and persistence of antibody secreting cells (ASC) after antigenic challenge remain inadequately understood in teleosts. In this study, intraperitoneal (ip) injection of Atlantic ...salmon (Salmo salar) with salmonid alphavirus (WtSAV3) increased the total ASC response, peaking 3–6 weeks post injection (wpi) locally in the peritoneal cavity (PerC) and in systemic lymphoid tissues, while at 13 wpi the response was only elevated in PerC. At the same time point a specific ASC response was induced by WtSAV3 in PerC and systemic tissues, with the highest frequency in PerC, suggesting a local role. Inactivated SAV (InSAV1) induced comparatively lower ASC responses in all sites, and specific serum antibodies were only induced by WtSAV3 and not by InSAV1. An InSAV1 boost did not increase these responses. Expression of immune marker genes implies a role for PerC adipose tissue in the PerC immune response. Overall, the study suggests the Atlantic salmon PerC as a secondary immune site and an ASC survival niche.
•Infection with salmonid alphavirus induced a specific IgM secreting cell response.•The local B cell response in the peritoneal cavity was pronounced and long lasting.•Gene expression suggests peritoneal adipose tissue is involved in the B cell response.•The B cell response to inactivated virus was modest or absent, also after a boost.
Infection is restrained by the concerted activation of tissue-resident and circulating immune cells. Whether tissue-resident lymphocytes confer early antiviral immunity at local sites of primary ...infection prior to the initiation of circulating responses is not well understood. Furthermore, the kinetics of initial antiviral responses at sites of infection remain unclear. Here, we show that tissue-resident type 1 innate lymphoid cells (ILC1) serve an essential early role in host immunity through rapid production of interferon (IFN)-γ following viral infection. Ablation of Zfp683-dependent liver ILC1 lead to increased viral load in the presence of intact adaptive and innate immune cells critical for mouse cytomegalovirus (MCMV) clearance. Swift production of interleukin (IL)-12 by tissue-resident XCR1+ conventional dendritic cells (cDC1) promoted ILC1 production of IFN-γ in a STAT4-dependent manner to limit early viral burden. Thus, ILC1 contribute an essential role in viral immunosurveillance at sites of initial infection in response to local cDC1-derived proinflammatory cytokines.
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•ILC1 represent the major early source of IFN-γ in virally infected tissues•ILC1-derived IFN-γ limits early MCMV replication in primary infected tissues•Crosstalk between cDC1 and ILC1 populations mediate initial local control of virus•ILC1 display enhanced responsiveness to IL-12 compared to other lymphocytes
Innate lymphoid cells have a non-redundant role as initial responders to viral infections.
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