Tissues Use Resident Dendritic Cells and Macrophages to Maintain Homeostasis and to Regain Homeostasis upon Tissue Injury: The Immunoregulatory Role of Changing Tissue Environments

Most tissues harbor resident mononuclear phagocytes, that is, dendritic cells and macrophages. A classification that sufficiently covers their phenotypic heterogeneity and plasticity during homeostasis and disease does not yet exist because cell culture-based phenotypes often do not match those found in vivo. The plasticity of mononuclear phagocytes becomes obvious during dynamic or complex disease processes. Different data interpretation also originates from different conceptual perspectives. An immune-centric view assumes that a particular priming of phagocytes then causes a particular type of pathology in target tissues, conceptually similar to antigen-specific T-cell priming. A tissue-centric view assumes that changing tissue microenvironments shape the phenotypes of their resident and infiltrating mononuclear phagocytes to fulfill the tissue's need to maintain or regain homeostasis. Here we discuss the latter concept, for example, why different organs host different types of mononuclear phagocytes during homeostasis. We further discuss how injuries alter tissue environments and how this primes mononuclear phagocytes to enforce this particular environment, for example, to support host defense and pathogen clearance, to support the resolution of inflammation, to support epithelial and mesenchymal healing, and to support the resolution of fibrosis to the smallest possible scar. Thus, organ- and disease phase-specific microenvironments determine macrophage and dendritic cell heterogeneity in a temporal and spatial manner, which assures their support to maintain and regain homeostasis in whatever condition. Mononuclear phagocytes contributions to tissue pathologies relate to their central roles in orchestrating all stages of host defense and wound healing, which often become maladaptive processes, especially in sterile and/or diffuse tissue injuries

Zastosowanie uszypułowanego płata skórno-mięśniowego z mięśnia czworobocznego w leczeniu zaburzenia gojenia rany pooperacyjnej po dwuetapowej stabilizacji kręgosłupa piersiowego – opis przypadku

Musculocutaneous flaps play an important role in modern reconstructive surgery. They are useful in the treatment of primary traumatic skin lesions and secondary lesions formed during complicated healing of the surgical wounds. The case of 60 years old woman undergoing complicated healing of the wound after spine surgery is presented. The patient was qualified to spine surgery due to metastatic tumour caused by the lung cancer. The use of pedicled flap facilitated healing of the wound; thus, there was no need to remove implants stabilising pathologically fractured spine. The issue of ‘reconstructive ladder’ is discussed in the paper with various treatment options. Indications, surgical technique and postoperative care are thoroughly discussed providing an overview on this valuable method of treatment which allows a successful termination of complicated wound healing process.We współczesnej medycynie płaty uszypułowane pełnią ważną rolę, zarówno w leczeniu pierwotnych – urazowych ubytków powłok ciała, jak również wtórnych do leczenia operacyjnego, powikłanych wadliwym gojeniem rany. Poniżej przedstawiamy przypadek 60-letniej kobiety z chorobą nowotworową ze złamaniem patologicznym kręgosłupa i źle gojącą się raną pooperacyjną. Zastosowanie płata uszypułowanego umożliwiło zamknięcie i wygojenie rany, co pozwoliło uniknąć konieczności usunięcia implantów stabilizujących złamany kręgosłup. Artykuł ten dotyka problemu drabiny rekonstrukcyjnej i odpowiada na pytanie, kiedy zastosować jaką metodę leczenia. Mówi o wskazaniach do wykonania zabiegu przeniesienia płata skórno-mięśniowego, postępowaniu okołooperacyjnym oraz opiece pooperacyjnej. Opisuje przydatną metodę leczniczą, której znajomość i umiejętność zastosowania pozwala zakończyć z sukcesem powikłany proces gojenia rany pooperacyjnej

Transcatheter closure of iatrogenic perimembranous ventricular septal defect after aortic valve and ascending aorta replacement using an Amplatzer membranous ventricular septal occluder

Iatrogenic perimembranous ventricular septal defect is a rare complication after surgical replacement of the aortic valve, and so transcatheter closure of such a defect is not a routine procedure. We report the successful closure of an iatrogenic perimembranous ventricular septal defect which occurred after the replacement of the aortic valve and ascending aorta. (Cardiol J 2008; 15: 189-191

Badanie metodą jednostopniowej amplifikacji kwasu nukleinowego węzłów chłonnych w raku brodawkowatym tarczycy — porównanie z badaniem histopatologicznym i badaniem PCR w czasie rzeczywistym

Introduction: The significance of lymph node metastases and the optimal extent of lymphadenectomy remain matters of controversy in papillary thyroid cancer. This study was designed to assess the feasibility and reliability of OSNA and real-time PCR for CK19 and TG mRNA in papillary thyroid cancer lymph nodes evaluation compared to standard histopathology.Material and methods: Each of 92 randomised lymph nodes from 32 papillary thyroid cancer patients were divided into representative parts and assessed using the three studied methods.Results: Eighteen (19.6%) lymph nodes from ten (31.3%) patients were positive according to histopathology. When the cut-off value distinguishing metastatic from non-metastatic lymph nodes in the OSNA assay was set at 250 copies per microlitre, the results were positive in 16 (17.4%) lymph nodes from 11 (34.4%) patients. Twenty three (25%) lymph nodes were tested positive in real-time PCR for TG mRNA. Real-time PCR for CK19 mRNA was positive in 18 (19.6%) lymph nodes from 13 (40.6%) patients. No statistically significant differences were noted between the diagnostic accuracy of either molecular method compared to the histopathological examination (p = 0.81). Overall, 20 positive molecular biology results were noted in patients with negative histopathology results. Conversely, in 18 lymph nodes, despite a metastasis finding in histopathology, at least one molecular test yielded a negative result.Conclusions: It was revealed that OSNA is a reliable technique for the evaluation of lymph node metastases in papillary thyroid cancer. This method was shown to have equivalent accuracy to histopathology and real-time PCR. (Endokrynol Pol 2014; 65 (6): 422–430)Wstęp: Znaczenie przerzutów do węzłów chłonnych oraz optymalny zakres limfadenektomii w raku brodawkowatym tarczycy pozostaje przedmiotem kontrowersji. Celem pracy była ocena wykonalności oraz zgodności wyników jednostopniowej amplifikacji kwasu nukleinowego oraz PCR w czasie rzeczywistym dla CK19 i TG mRNA w badaniu węzłów chłonnych w raku brodawkowatym tarczycy w porównaniu z rutynowym badaniem histopatologicznym.Materiał i metody: Każdy z 92 węzłów chłonnych pochodzących od 32 pacjentów z rakiem brodawkowatym tarczycy został podzielony na reprezentatywne części i zbadany trzema metodami.Wyniki: Osiemnaście (19,6%) węzłów chłonnych od 10 (31,3%) pacjentów miało dodatni wynik badania histopatologicznego. Przyjmując wartość odcięcia 250 kopii w mikrolitrze, różnicującej węzły chłonne zmienione przerzutowo od niezmienionych, w badaniu jednoetapowej amplifikacji kwasu nukleinowego, stwierdzono dodatni wynik badania w 16 (17,4%) węzłach chłonnych od 11 (34,4%) pacjentów. Uzyskano dodatni wynik badania PCR w czasie rzeczywistym dla TG mRNA w 23(25%) węzłach chłonnych, natomiast dla CK19 mRNA w 18 (19,6%) od 13 (40,6%) pacjentów. Nie stwierdzono istotnej statystycznie różnicy pomiędzy zgodnością wyników obu metod molekularnych z wynikiem badania histopatologicznego (p = 0,81). Ogólnie stwierdzono 20 dodatnich wyników badania molekularnego z węzłów chłonnych, przy ujemnym wyniku badania histopatologicznego. Natomiast w 18 węzłach, pomimo znalezienia przerzutów w badaniu histopatologicznym, uzyskano ujemny wynik w przynajmniej jednym badaniu molekularnym.Wnioski: Badanie jednostopniową amplifikacją kwasu nukleinowego jest właściwą metodą oceny obecności przerzutów w węzłach chłonnych w raku brodawkowatym tarczycy. Technika ta ma zbliżona wiarygodność do badania histopatologicznego i badania PCR w czasie rzeczywistym. (Endokrynol Pol 2014; 65 (6): 422–430

Quantitative Expression of C-Type Lectin Receptors in Humans and Mice

C-type lectin receptors, their adaptor molecules and S-type lectins (galectins) are involved in the recognition of glycosylated self-antigens and pathogens. However, little is known about the species- and organ-specific expression profiles of these molecules. We therefore determined the mRNA expression levels of Dectin-1, MR1, MR2, DC-SIGN, Syk, Card-9, Bcl-10, Malt-1, Src, Dec-205, Galectin-1, Tim-3, Trem-1, and DAP-12 in 11 solid organs of human and mice. Mouse organs revealed lower mRNA levels of most molecules compared to spleen. However, Dec-205 and Galectin-1 in thymus, Src in brain, MR2, Card-9, Bcl-10, Src, and Dec-205 in small intestine, MR2, Bcl-10, Src, Galectin-1 in kidney, and Src and Galectin-1 in muscle were at least 2-fold higher expressed compared to spleen. Human lung, liver and heart expressed higher mRNA levels of most genes compared to spleen. Dectin-1, MR1, Syk and Trem-1 mRNA were strongly up-regulated upon ischemia-reperfusion injury in murine kidney. Tim3, DAP-12, Card-9, DC-SIGN and MR2 were further up-regulated during renal fibrosis. Murine kidney showed higher DAP-12, Syk, Card-9 and Dectin-1 mRNA expression during the progression of lupus nephritis. Thus, the organ-, and species-specific expression of C-type lectin receptors and galectins is different between mice and humans which must be considered in the interpretation of related studies

Toll-Like Receptor and Accessory Molecule mRNA Expression in Humans and Mice as Well as in Murine Autoimmunity, Transient Inflammation, and Progressive Fibrosis

The cell type-, organ-, and species-specific expression of the Toll-like receptors (TLRs) are well described, but little is known about the respective expression profiles of their accessory molecules. We therefore determined the mRNA expression levels of LBP, MD2, CD36, CD14, granulin, HMGB1, LL37, GRP94, UNC93b1, TRIL, PRAT4A, AP3B1, AEP and the respective TLRs in human and mouse solid organs. Humans and mice displayed significant differences between their respective mRNA expression patterns of these factors. In addition, the expression profiles in transient tissue inflammation upon renal ischemia-reperfusion injury, in spleens and kidneys from mice with lupus-like systemic autoimmunity, and in progressive tissue fibrosis upon unilateral ureteral obstruction were studied. Several TLR co-factors were specifically regulated during the different phases of these disease entities, suggesting a functional involvement in the disease process. Thus, the organ-and species-specific expression patterns need to be considered in the design and interpretation of studies related to TLR-mediated innate immunity, which seems to be involved in the tissue injury phase, in the phase of tissue regeneration, and in progressive tissue remodelling