CD45+, CD68+ and E-cadherin+ Expressions in Skin Dogs Naturally Infected by Leishmania infantum

Background: In canine leishmaniasis (CanL), infection occurs through phlebotomine vectors that inoculate the protozoan Leishmania infantum into the skin that infected macrophages and activated dendritic cells (CD). Dogs with CanL present variable clinical manifestations, being common the presence of cutaneous lesions. The aim of this study was to evaluate the expression of CD45+, CD68+ and E-cadherin+  associating the skin sentinels cells and to compare the clinical-dermatological manifestations in the skin of dogs naturally infected by L. infantum.Materials, Methods & Results: Dogs infected (n = 22) by L. infantum were divided into asymptomatic group (AD, n = 9), and symptomatic group (SD, n = 13), according criteria based on the presence or absence of skin changes. Dogs non-infected (CD, n = 5) were included as control group. Samples of skin biopsies collected from scapular region were processed by routine histology and labeled by immunohistochemistry with monoclonal antibodies against CD45+, CD68+ and E-cadherin+, and were described as none, mild, moderate and intense. SD presented keratoconjunctivitis, onychogryphose, lichenification, depigmentation, alopecia, hypotrichosis, erythematous dermatitis, exfoliative dermatitis, ulcerative dermatitis and crusted dermatitis, and the frequency these alterations was expressed as percentage. The results of hematological and biochemical parameters were analyzed by Kruskal-Wallis test followed by the Dunn’s test and expressed as mean ± standard deviation, with values P < 0.05. Leukocytosis (not significant), red blood cells, hematocrit and hemoglobin (P < 0.05), total protein serum (P < 0.05), globulins (P < 0.05), albumin and A/G ratio (P < 0.01) were altered in SD in relation to CD. Cutaneous cellular infiltration, composed by macrophages, plasma cells, lymphocytes and neutrophils, was observed in CD. There was an increase of expression of the markers in SD when compared to the other groups, as moderate CD68+ expression and L. infantum, and intense CD45+ and E-cadherin+ expressions.Discussion: Cutaneous involvement is very important in CanL, as it corresponds to where is the first interaction between the parasite and the immune system. Dermatological clinical signs, leukocytosis, anemia, globulins levels have been reported for dogs naturally infected by L. infantum. Inflammatory infiltrate was distributed at superficial and deep dermis, which was composed by mononuclear cells as macrophages, plasma cells, lymphocytes and neutrophils. To characterize the immune sentinels cells in the skin it was evaluated CD45+, CD68+ and E-cadherin+ expressions. In syntomatic dogs, our results revelead an increase of expression of these markers. CD45+ is one of the most abundant molecules expressed on the white blood cell surface in various mammals, while CD68+ is a myelomonocytic marker that seems to be retained during monocyte differentiation. In the skin, increased numbers of CD68+ are related to dendritic epidermal cells, which can be expressed as CD45+/CD1a-/HLA-DR+. DCs of the skin, particularly epidermal Langerhans cells (LCs), form networks anchored to neighboring keratinocytes via E-cadherin. Thus, CD45+, CD68+ and E-cadherin+ expressions may be related to activation of skin sentinels cells in dogs naturally infected by L. infantum. Our results indicated that CanL modify the CD45+, CD68+ and E-cadherin+ expressions, which characterize the immune sentinels cells activation that promove the recruitment the cellular infiltrate, which was composed by macrophages, plasma cells, lymphocytes and neutrophils. Thus, these informations may contribute to the follow-up of CanL progression in skin

ENVOLVIMENTO DA MATRIZ EXTRACELULAR NO TUMOR MAMÁRIO CANINO

Mammary gland (MG) is a dynamic tissue derived from the epidermis and your development depends on the interaction between mammary cells and stroma. Extracellular matrix (ECM) is the major extracellular content of tissues responsible for supporting connective tissue and basement membrane, and serves as a reservoir for many growth factors. ECM is comprised of insoluble protein fibers as collagens, laminins, fibronectins and soluble polymers as proteoglycans, and glycosaminoglycans. The ECM components are important both during morphogenesis of MG as to maintain this fabric giving support and storage of substrates needed for the growth. ECM disorder in GM may be the progression trigger of the breast tumor. Canine mammary tumor (CMT) is a complex of malignancies that have the participation of several factors for its development, including ECM components. Therefore an investigation of ECM in the diagnosis of CMT becomes important to establish a relationship between componentes of matrix and neoplastic cells, including information on the biological behavior and clinical staging of CMT. The knowledge of ECM molecules participation in the development of CMT may further therapeutic approaches targeting elements of ECM. Thus, this review has a focus on the ECM components participation in the processes that contribute to CMT establishment, which may favor therapeutic approaches targeting elements of ECM.A glândula mamária (GM) é um tecido dinâmico, derivado da epiderme e o seu desenvolvimento depende da interação entre as células mamárias e o estroma. A matriz extracelular (MEC) representa o principal conteúdo extracelular, responsável pela sustentação do tecido conjuntivo, da membrana basal e serve como reservatório para muitos fatores de crescimento. MEC é constituída por fibras proteicas insolúveis, como colágenos, lamininas, fibronectinas, e polímeros solúveis, como proteoglicanos e glicosaminoglicanos. Essas moléculas que compõem a MEC são importantes, tanto durante a morfogênese da GM, como para a sua manutenção conferindo-lhe a sustentação e o armazenamento de substratos necessários para seu crescimento. A desorganização da MEC na GM pode ser um indício necessário para o início e a progressão do tumor de mama. O Tumor mamário canino (TMC) é referido como um complexo de neoplasias que tem a participação de diversos fatores para seu desenvolvimento, incluindo os componentes da MEC. Desta forma, a investigação da MEC no diagnóstico dos TMC torna-se importante, para estabelecer a correlação entre os seus componentes e as células neoplásicas, além de fornecer informações sobre o comportamento biológico e o estadiamento clínico dos TMC. O entendimento da participação dessas moléculas da MEC para o desenvolvimento do TMC pode favorecer abordagens terapêuticas mais específicas, tendo como alvo elementos da MEC. Portanto, esta revisão tem como foco a participação dos componentes da MEC nos processos que contribuem para o estabelecimento do TMC, o que pode favorecer abordagens terapêuticas que visem elementos da MEC