Developmental origin and maintenance of distinct testicular macrophage populations

International audienceTesticular macrophages (tM phi) are the principal immune cells of the mammalian testis. Beyond classical immune functions, they have been shown to be important for organogenesis, spermatogenesis, and male hormone production. In the adult testis, two different macrophage populations have been identified based on their distinct tissue localization and morphology, but their developmental origin and mode of homeostatic maintenance are unknown. In this study, we use genetic lineage-tracing models and adoptive transfer protocols to address this question. We show that embryonic progenitors give rise to the interstitial macrophage population, whereas peritubular macrophages are exclusively seeded postnatally in the prepuberty period from bone marrow (BM)-derived progenitors. As the proliferative capacity of interstitial macrophages declines, BM progenitors also contribute to this population. Once established, both the peritubular and interstitial macrophage populations exhibit a long life span and a low turnover in the steady state. Our observations identify distinct developmental pathways for two different tM phi populations that have important implications for the further dissection of their distinct roles in organ homeostasis and testicular function

Antagonizing retinoic acid receptors increases myeloid cell production by cultured human hematopoietic stem cells

Activities of the retinoic acid receptor (RAR)α and RARγ are important to hematopoiesis. Here, we have investigated the effects of receptor selective agonists and antagonists on the primitive human hematopoietic cell lines KG1 and NB-4 and purified normal human hematopoietic stem cells (HSCs). Agonizing RARα (by AGN195183) was effective in driving neutrophil differentiation of NB-4 cells and this agonist synergized with a low amount (10 nM) of 1α,25-dihydroxyvitamin D(3) to drive monocyte differentiation of NB-4 and KG1 cells. Treatment of cultures of human HSCs (supplemented with stem cell factor ± interleukin 3) with an antagonist of all RARs (AGN194310) or of RARα (AGN196996) prolonged the lifespan of cultures, up to 55 days, and increased the production of neutrophils and monocytes. Slowing down of cell differentiation was not observed, and instead, hematopoietic stem and progenitor cells had expanded in number. Antagonism of RARγ (by AGN205728) did not affect cultures of HSCs. Studies of CV-1 and LNCaP cells transfected with RAR expression vectors and a reporter vector revealed that RARγ and RARβ are activated by sub-nM all-trans retinoic acid (EC(50)–0.3 nM): ~50-fold more is required for activation of RARα (EC(50)–16 nM). These findings further support the notion that the balance of expression and activity of RARα and RARγ are important to hematopoietic stem and progenitor cell expansion and differentiation

Perivascular macrophages in health and disease

Macrophages are a heterogeneous group of cells that are capable of carrying out distinct functions in different tissues, as well as in different locations within a given tissue. Some of these tissue macrophages lie on, or close to, the outer (abluminal) surface of blood vessels and perform several crucial activities at this interface between the tissue and the blood. In steady-state tissues, these perivascular macrophages maintain tight junctions between endothelial cells and limit vessel permeability, phagocytose potential pathogens before they enter tissues from the blood and restrict inappropriate inflammation. They also have a multifaceted role in diseases such as cancer, Alzheimer disease, multiple sclerosis and type 1 diabetes. Here, we examine the important functions of perivascular macrophages in various adult tissues and describe how these functions are perturbed in a broad array of pathological conditions

Hockey: a pain in the butt! Isolated superior gluteal artery rupture following blunt pelvic trauma - an unusual case

Superior gluteal artery rupture is a rare complication of trauma but a significant one with potential for substantial morbidity and mortality. This case demonstrates the importance of early diagnosis and treatment of this injury pattern. Endovascular embolisation has become the most effective treatment for pelvic haemorrhage. Acknowledgement of this rare injury as a differential diagnosis is vital to facilitate rapid diagnosis and appropriate treatment.The article is available via Open Access. Click on the 'Additional link' above to access the full-text.Not permitte

A Survey on Lead and Cadmium Content in Bread Produced in Yazd

Introduction: Due to such complications of absorbing lead and cadmium heavy metals as kidney and liver dysfunction, vascular and heart diseases, anemia, digestive complications, nervous and skeletal problems and due to importance of bread as one of the most important food diets in Iran, especially in Yazd, the amount of lead and cadmium was evaluated in a variety of breads in Yazd. Methods: This descriptive cross-sectional study was carried out in 2013. Out of 69 bakeries, random probability proportionate sampling was applied in order to measure the heavy metals (lead and cadmium content) in samples by ash and atomic absorption equipped with grafiti furnace(ETAAS) with correction of background time. The study data were analyzed using SPSS (v.17) considering p-value of less than 0.05 as significant. Results: The average amounts of lead and cadmium were 99.05 and 7.49 mg/kg respectively. The amount of lead in Sangak bread was higher than that of other types of breads, whereas lead amounts of fantasy bread was reported less than those of other breads. Cadmium content demonstrated no significant differences among breads. Lead amount was higher in direct heat breads. Whereas, cadmium amount showed no significant differences between direct and indirect heat breads. It is worth mentioning that lead and cadmium content were reported lower than allowable levels in all samples. Conclusions: As the study results revealed and considering per capita consumption of bread in Iran (about 160 kg), it seems that weekly intake of lead and cadmium in Yazd is at an acceptable level, though possible risk of heavy metals(lead and cadmium) need to decrease in order to prevent the probable risks of lead and cadmium heavy metals

Development of Macrophages with Altered Actin Organization in the Absence of MafB

In the hematopoietic system the bZip transcription factor MafB is selectively expressed at high levels in monocytes and macrophages and promotes macrophage differentiation in myeloid progenitors, whereas a dominant-negative allele can inhibit this process. To analyze the requirement of MafB for macrophage development, we generated MafB-deficient mice and, due to their neonatal lethal phenotype, analyzed macrophage differentiation in vitro, in the embryo, and in reconstituted mice. Surprisingly we observed in vitro differentiation of macrophages from E14.5 fetal liver (FL) cells and E18.5 splenocytes. Furthermore we found normal numbers of F4/80(+)/Mac-1(+) macrophages and monocytes in fetal liver, spleen, and blood as well as in bone marrow, spleen, and peritoneum of adult MafB(−/−) FL reconstituted mice. MafB(−/−) macrophages showed intact basic macrophage functions such as phagocytosis of latex beads or Listeria monocytogenes and nitric oxide production in response to lipopolysaccharide. By contrast, MafB(−/−) macrophages expressed increased levels of multiple genes involved in actin organization. Consistent with this, phalloidin staining revealed an altered morphology involving increased numbers of branched protrusions of MafB(−/−) macrophages in response to macrophage colony-stimulating factor. Together these data point to an unexpected redundancy of MafB function in macrophage differentiation and a previously unknown role in actin-dependent macrophage morphology

Singlemode chalcogenide fiber infrared SNOM probes

We have fabricated and tested infrared scanning near-field optical microscope (IR-SNOM) probe tips made from singlemode chalcogenide fiber. The process used to create the tips was similar to conventional micropipette-puller techniques, with some modifications to allow for the lower melting temperature and tensile strength of the chalcogenide fiber. SEM micrographs, showing tips with sub-micrometer physical dimensions, demonstrate the feasibility of this process. Topographical data obtained using a shear-force near-field microscope exhibits spatial resolution in the range 80-100 nm. Optical data in the infrared (near 3.5 mu m), using the probe tips in collection mode, indicates an optical spatial resolution approximately lambda/15. (C) 1999 Published by Elsevier Science B.V. hll rights reserved