Monocyte and macrophage subtypes as paired cell biomarkers for coronary artery disease.

NEW FINDINGS: What is the central question of this study? Are circulating monocyte markers correlated with their derived macrophage polarization patterns and coronary artery disease severity? What is the main finding and its importance? There was an inverse relationship between circulating CD16+ monocytes (high) and M2 macrophages (low) that marked coronary disease severity, and the differences in polarization of macrophages were seen despite a week of cell culture ex vivo. This study highlights the importance, and potential prognostic implications, of circulating monocyte and descendant macrophage phenotypes in coronary artery disease. ABSTRACT: Monocytes and macrophages are central to atherosclerosis, but how they combine to mark progression of human coronary artery disease (CAD) is unclear. We tested whether patients' monocyte subtypes paired with their derived macrophage profiles were correlated with extent of CAD. Peripheral blood was collected from 40 patients undergoing cardiac catheterization, and patients were categorized as having no significant CAD, single vessel disease or multivessel disease according to the number of affected coronary arteries. Mononuclear cells were measured for the monocyte markers CD14 and CD16 by flow cytometry, and separate monocytes were cultured into macrophages over 7 days and measured for the polarization markers CD86 and CD206. At baseline, patients with a greater CAD burden were older, with higher rates of statin, ß-blocker and antiplatelet drug use, whereas other characteristics were similar across the spectrum of coronary disease. CD16+ (both intermediate and non-classical) monocytes were elevated in patients with single vessel and multivessel disease compared with those without significant CAD (P < 0.05), whereas regulatory M2 macrophages (CD206+ ) were decreased in patients with single vessel and multivessel disease (P < 0.001). An inverse relationship between paired CD16+ monocytes and M2 macrophages marked CAD severity. On multivariable linear regression, CAD severity was associated, along with age and traditional cardiovascular risk factors, with CD16+ monocytes (directly) and M2 macrophages (inversely). Circulating monocytes may influence downstream polarization of lesional macrophages, and these measures of monocyte and macrophage subtypes hold potential as biomarkers in CAD.

Acrochordon With Histological Features of Lichen Sclerosus.

Lichen sclerosus (LS) is a chronic inflammatory dermatosis that classically presents as sclerotic, atrophic plaques in the genital region. We present a case of acrochordon with histological features of LS, clinically mimicking intradermal nevus, in a 53-year-old man with no prior history of LS. Our case highlights an unusual morphologic variant of acrochordon and illustrates the role of chronic pressure and occlusion in the development of secondary features of LS.

A review of cutaneous hypersensitivity reactions in infants: From common to concerning.

Cutaneous hypersensitivity reactions in infants present in a variety of patterns. These skin eruptions can be dramatic, causing alarm in parents and medical personnel. Many of these syndromes have overlapping features, which adds to the confusion and uncertainty regarding diagnosis and management. This review discusses the spectrum of hypersensitivity responses with a focus on their presentation in infants. The clinical findings, pathophysiology, histopathology, management, and complications of these conditions will be reviewed.

Maternal Inflammation Disrupts Fetal Neurodevelopment via Increased Placental Output of Serotonin to the Fetal Brain.

UNLABELLED: Maternal inflammation during pregnancy affects placental function and is associated with increased risk of neurodevelopmental disorders in the offspring. The molecular mechanisms linking placental dysfunction to abnormal fetal neurodevelopment remain unclear. During typical development, serotonin (5-HT) synthesized in the placenta from maternal l-tryptophan (TRP) reaches the fetal brain. There, 5-HT modulates critical neurodevelopmental processes. We investigated the effects of maternal inflammation triggered in midpregnancy in mice by the immunostimulant polyriboinosinic-polyribocytidylic acid [poly(I:C)] on TRP metabolism in the placenta and its impact on fetal neurodevelopment. We show that a moderate maternal immune challenge upregulates placental TRP conversion rapidly to 5-HT through successively transient increases in substrate availability and TRP hydroxylase (TPH) enzymatic activity, leading to accumulation of exogenous 5-HT and blunting of endogenous 5-HT axonal outgrowth specifically within the fetal forebrain. The pharmacological inhibition of TPH activity blocked these effects. These results establish altered placental TRP conversion to 5-HT as a new mechanism by which maternal inflammation disrupts 5-HT-dependent neurogenic processes during fetal neurodevelopment. SIGNIFICANCE STATEMENT: The mechanisms linking maternal inflammation during pregnancy with increased risk of neurodevelopmental disorders in the offspring are poorly understood. In this study, we show that maternal inflammation in midpregnancy results in an upregulation of tryptophan conversion to serotonin (5-HT) within the placenta. Remarkably, this leads to exposure of the fetal forebrain to increased concentrations of this biogenic amine and to specific alterations of crucially important 5-HT-dependent neurogenic processes. More specifically, we found altered serotonergic axon growth resulting from increased 5-HT in the fetal forebrain. The data provide a new understanding of placental function playing a key role in fetal brain development and how this process is altered by adverse prenatal events such as maternal inflammation. The results uncover important future directions for understanding the early developmental origins of mental disorders.