The Origin and Function of Langerin (CD207) Expressing Cells in Mice and Humans

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. SCI-7-SCI-7
Author(s):  
Miriam Merad

Abstract Abstract SCI-7 The current paradigm suggests that Langerhans cell histiocytosis (LCH) results from an accumulation of epidermal dendritic cells also called Langerhans cells. This concept is based on phenotypic and ultrastructural observations showing that LCH lesions are infiltrated by CD1a+langerin+ cells, two features thought to be restricted to epidermal Langerhans cells. It has been difficult, however, to understand how Langerhans cells, which are normally restricted to stratified epithelia, could give rise to such a multifocal disorder. LCH research has been handicapped by the inability to develop reliable animal models and by the fact that for a long time very few markers were available to determine the origin and stage of differentiation of histiocytes, now renamed macrophage/dendritic cell lineages. This presentation will discuss recent progress in our understanding of the regulation of the Langerhans cell, macrophage, and dendritic cell lineages and discuss the relationship of these lineages with the LCH cell. Disclosures: No relevant conflicts of interest to declare.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. SCI-8-SCI-8
Author(s):  
Carl E. Allen

Abstract Abstract SCI-8 Langerhans cell histiocytosis (LCH) is a disorder characterized by inflammatory lesions that include pathologic CD207+ dendritic cells. LCH has pleotropic clinical presentations ranging from single lesions cured by curettage to potentially fatal multisystem disease. The first descriptions of LCH, including Hand-Schüller-Christian disease and Letterer-Siwe disease, were based on anatomic location and extent of the lesions. Despite clinical heterogeneity, LCH lesions are generally indistinguishable by histology, which led to the notion that the spectrum of clinical manifestations represents a single disorder, histiocytosis X. The designation “Langerhans cell histiocytosis” was subsequently proposed with discovery of cytoplasmic Birbeck granules in the pathologic infiltrating dendritic cells in histiocytosis X lesions, a feature shared by epidermal Langerhans cells. The etiology of LCH remains elusive, and debate of LCH as an inflammatory versus malignant disorder remains unresolved. However, recent discoveries question the model of LCH arising from transformed or pathologically activated epidermal Langerhans cells. We found cell-specific gene expression signature in CD207+ dendritic cells within LCH lesions to be more consistent with immature myeloid dendritic cell precursors than epidermal Langerhans cells. Furthermore, recent mouse studies demonstrate that CD207+ is more promiscuous than previously appreciated. Langerin (CD207) expression can be induced in many dendritic cell lineages, supporting the plausibility of a spectrum of candidates for an LCH cell of origin, including circulating dendritic cell precursors. Finally, recurrent activating BRAF mutations in LCH lesions suggest a role for a hyperactive RAS pathway in LCH pathogenesis, and possibly in normal dendritic cell development. This presentation will discuss the historical background and recent advances in LCH biology, along with a proposal to reframe “histiocytosis X” as a myeloid neoplasia caused by aberrant maturation and migration of myeloid dendritic cell precursors. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4716-4716
Author(s):  
Baptiste Hervier ◽  
Julien Haroche ◽  
Olivier Hermine ◽  
Jean Donadieu ◽  
Frederic Charlotte ◽  
...  

Abstract Abstract 4716 Objectives Histiocytoses are a heterogeneous group of diseases that can be classified into either Langerhans cell histiocytosis (LCH) or non-Langerhans cell histiocytosis. The latter includes Erdheim-Chester disease (ECD). This study investigated the clinical association between LCH and ECD. Methods This retrospective study included 16 patients (10 males, 6 females, median age 41 years) treated at twelve different university hospitals between 1970 and 2010. Inclusion criteria were biopsy-proven LCH in association with two or more diagnostic signs of ECD. Results LCH and ECD were diagnosed simultaneously in 4/16 cases, whereas LCH preceded ECD in 12/16 cases. The median time interval was 7.5 years (range 2–22) in these cases. Major organs involved in LCH were the bones (n=12), skin (n=8) and lungs (n=3). ECD mainly affected the large vessels (n=11), bones (n=11) and retroperitoneum (n=9). Non-biopsy proven central nervous system (n=6) and pituitary gland (n=6) involvement also occurred. No specific histologic features were identified in the 65 biopsies studied, including platelet-derived growth factor receptor β expression. Between one and four lines of treatment were required in nine patients diagnosed with LCH. Nine patients were treated with interferon α-2a after the diagnosis of ECD was made. A partial improvement occurred in all assessable patients concerning ECD (n=5) and/or LCH (n=2). These 16 patients were compared with a monocentric cohort of 48 ECD patients; the only difference between the groups was a lower frequency of bone involvement in ECD patients with concomitant LCH (9/13 vs 47/48, p<0.003). Conclusions This study suggests that a pathogenic link exists between LCH and ECD. Although the mechanisms responsible for both diseases remain unknown, the present association could argue for transitions between monocyte/macrophage and dendritic cell lineages. The patient characteristics of LCH in association with ECD were similar to those in patients with LCH alone, whereas bone involvement may have been less common in ECD when it was in association with LCH. Clinicians should be aware of this association and should consider the possibility of ECD in patients with LCH, especially in the case of treatment resistance. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
1948 ◽  
Vol 3 (7) ◽  
pp. 729-754 ◽  
Author(s):  
WILLIAM N. VALENTINE ◽  
CHARLES G. CRADDOCK ◽  
JOHN S. LAWRENCE

Abstract The hormonal control through the hypophyseo-adrenal cortical system of lymphoid tissue structure and function is an important concept. We cannot at the present time regard that the concept is established fact. Final judgment must await additional work and the clarification of some of the inconsistencies which appear to exist. It seems reasonable that lymphoid tissue is one of the end organs of adrenal cortical hormone and that it may perhaps play a role in the response of the organism to stress. It seems quite clear that the sugar hormone of the adrenal cortex is capable of producing structural alterations in lymphoid tissue. Change in thoracic duct lymphocyte numbers as a result of augmentation in the amount of available adrenal cortical hormone is at present controversial. Experiments in this laboratory have failed to demonstrate it. The production of lymphopenia, at least in some species and possibly in man, by increasing available sugar hormone is supported by some evidence. The exact mechanism of production of lymphopenia is open to question, its relationship to changes in lymphoid tissue structure being one of inference. The converse situation—absolute lympocytosis resulting from deprivation of adrenal cortical hormone—is the subject of controversial reports. At best, it must be admitted that relatively slight alterations from the accepted normal range of lymphocyte values occur in the adrenal insufficient organism. Changes in plasma gamma globulins and antibody titers associated with changes in the amount of available cortical hormone are reported. It should be clarified whether such changes have necessarily resulted from lymphocyte dissolution or are related to other of the variegated actions of adrenal cortical hormone. The relationship of adrenal cortical hormone to lymphoid tissue and lymphocytes and the relationship of the latter to the response of the organism to stress must indeed be complex. It is reasonably well established that the life span of the lymphocyte is very short indeed1,58,22 and each lymphocyte presumably liberates its metabolically important contents within a few hours at the most. If stress continues for any period of time, as often it does, it is difficult to visualize the wisdom of interfering with the production of metabolically vital substances in order to secure the transient benefits of lymphoid tissue dissolution. It is also somewhat difficult to regard as proved that the various changes reported after hormone augmentation or deprivation necessarily represent the normal mechanism by which these factors are regulated and kept within physiologic limits. More investigations are required to answer such questions and to further elucidate the interrelationship of the adrenal cortex and lymphoid tissues.


2013 ◽  
Vol 726-731 ◽  
pp. 1566-1572 ◽  
Author(s):  
Shi Qiang Ding ◽  
Qing Na Li ◽  
Xin Rong Pang ◽  
Ji Run Xu

The characteristics of flocs aggregated in flocculation have been paid more and more attention for a long time. In this paper, a new classification and analyses method dealing with the flocs is developed. The flocs formed after flocculation is divided into four kinds, including the left primary particles, linear flocs with all component particles in a line, planar flocs with all component particles on a plane and volumetric flocs with all component particles in a three-dimensional space. By analyzing the formation approaches of different kind of flocs regardless of the floc breakage, the number of every kind of floc is analyzed to be related with the suspension concentration mathematically. After comparing the different items in the models describing the relationship of floc number and concentration, a series of simplified expressions are presented. Lastly, a mathematical equation relating the measurable suspension viscosity with the numbers of different flocs is obtained.


Open Heart ◽  
2018 ◽  
Vol 5 (2) ◽  
pp. e000831 ◽  
Author(s):  
Melissa Suzanne Burroughs Peña ◽  
Katrina Swett ◽  
Robert C Kaplan ◽  
Krista Perreira ◽  
Martha Daviglus ◽  
...  

ObjectiveTo describe the relationship of household secondhand smoke (SHS) exposure and cardiac structure and function.MethodsParticipants (n=1069; 68 % female; age 45–74 years) without history of tobacco use, coronary artery disease or severe valvular disease were included. Past childhood (starting at age <13 years), adolescent/adult and current exposure to household SHS was assessed. Survey linear regression analyses were used to model the relationship of SHS exposure and echocardiographic measures of cardiac structure and function, adjusting for covariates (age, sex, study site, alcohol use, physical activity and education).ResultsSHS exposure in childhood only was associated with reduced E/A velocity ratio (β=−0.06 (SE 0.02), p=0.008). SHS exposure in adolescence/adult only was associated with increased left ventricular ejection fraction (LVEF) (1.2 (0.6), p=0.04), left atrial volume index (1.7 (0.8), p=0.04) and decreased isovolumic relaxation time (−0.003 (0.002), p=0.03). SHS exposure in childhood and adolescence/adult was associated with worse left ventricular global longitudinal strain (LVGLS) (two-chamber) (0.8 (0.4), p= 0.049). Compared with individuals who do not live with a tobacco smoker, individuals who currently live with at least one tobacco smoker had reduced LVEF (−1.4 (0.6), p=0.02), LVGLS (average) (0.9 (0.40), p=0.03), medial E′ velocity (−0.5 (0.2), p=0.01), E/A ratio (−0.09 (0.03), p=0.003) and right ventricular fractional area change (−0.02 (0.01), p=0.01) with increased isovolumic relaxation time (0.006 (0.003), p=0.04).ConclusionsPast and current household exposure to SHS was associated with abnormalities in cardiac systolic and diastolic function. Reducing household SHS exposure may be an opportunity for cardiac dysfunction prevention to reduce the risk of future clinical heart failure.


2019 ◽  
Vol 8 (9) ◽  
pp. 214-225
Author(s):  
Nongmeikapam Premika Devi

The present study examines the relationship of depression and the neuropsychologicalfunction of attention, planning and auditory verbal learning and memory among individualswith HIV/AIDS. 200 subjects who were HIV/AIDS positive (100 males and 100 females) andwere within age range of 20 to 50 years and minimum education level of 8th standard weretaken. The result indicates that Depression slows down the performance of attention; alsodepression most likely decreases the function of auditory verbal learning and memory


Perichoresis ◽  
2015 ◽  
Vol 13 (1) ◽  
pp. 75-97
Author(s):  
Laura Verner

Abstract An integral method of keeping a non-conforming community functioning is the construction and up keep of networks, as this web of connections provided security and protection with other non-conformists against the persecuting authorities. The non-conforming Catholic community of Elizabethan England (1558-1603) established various networks within England and abroad. This article is based on research that examines the network of Catholics in the Elizabethan Midlands in order to understand both its effectiveness and the relationship of the local and extended Catholic community with one another. The construction, function and result of these networks will be surveyed over several categories of networks, such as local, underground, clerical and exile. Members of the Midland Catholic community travelled to others areas of the British Isles and Europe to gather spiritual and material support for their faith, sent their children abroad for religious education, and resettled abroad creating in this wake a larger and complex international network. The main objective of this exercise is to show the dynamic and function of the network, and understand the impact it had at the local level for Midland Catholics.


Author(s):  
Мархат Увайсовна Яхьяева

В статье предпринята попытка соотношения таких юридических категорий, как «уголовное преследование» и «функция обвинения». Проводится компаративный анализ обвинения и подозрения как неотъемлемых элементов деятельности органов, осуществляющих уголовное преследование. The article attempts to correlate such legal categories as “criminal prosecution” and “function of accusation”. A comparative analysis of charges and suspicions as integral elements of the activities of bodies carrying out criminal prosecution is carried out.


1985 ◽  
Vol 73 (1) ◽  
pp. 299-310
Author(s):  
J.S. Hyams

Axonemes from the heterosporous water fern Marsilea vestita were fixed in the presence of tannic acid and examined by thin-section electron microscopy. Transverse sections revealed the normal 9+2 configuration except for the absence of the outer of the two dynein arms. Both arms were normally preserved in parallel preparations of Chlamydomonas axonemes. Isolated dynein from the ciliated protozoon Tetrahymena bound to Marsilea axonemes at the site normally occupied by the outer arm. Dynein binding was partially reversed by ATP as judged by both electron microscopy and polyacrylamide gel electrophoresis. This system should provide a valuable insight into the biochemistry and function of the inner dynein arm and the relationship of the two arms to motility in more conventionally equipped axonemes.


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