Marc Cloutier

Bio: Marc Cloutier is an academic researcher from Héma-Québec. The author has contributed to research in topics: Medicine & Lung. The author has an hindex of 10, co-authored 26 publications receiving 300 citations. Previous affiliations of Marc Cloutier include Laval University.

Tracheal occlusion: a review of obstructing fetal lungs to make them grow and mature.

Abstract: Fetal lung growth and functional differentiation are affected strongly by the extent that pulmonary tissue is distended (expanded) by liquid that naturally fills developing future airspaces Methods that prevent normal egress of this lung fluid through the trachea magnify mechanical stretching of lung parenchymal cells, thereby promoting lung development Indeed, experimental observations demonstrate that in utero tracheal occlusion (TO) performed on fetuses during the late canalicular-early saccular stage potently stimulates pulmonary growth and maturation In this review, we present the four principle non-human animal models of TO/obstruction and discuss them in relation to their utility in elucidating lung development, in remedying congenital diaphragmatic hernia (CDH) as well as in investigating the stretching effects on growth and remodeling of the fine vasculature

Major role of IgM in the neutralizing activity of convalescent plasma against SARS-CoV-2

Abstract: Characterization of the humoral response to SARS-CoV-2, the etiological agent of Covid-19, is essential to help control the infection. In this regard, we and others recently reported that the neutralization activity of plasma from COVID-19 patients decreases rapidly during the first weeks after recovery. However, the specific role of each immunoglobulin isotype in the overall neutralizing capacity is still not well understood. In this study, we selected plasma from a cohort of Covid-19 convalescent patients and selectively depleted immunoglobulin A, M or G before testing the remaining neutralizing capacity of the depleted plasma. We found that depletion of immunoglobulin M was associated with the most substantial loss of virus neutralization, followed by immunoglobulin G. This observation may help design efficient antibody-based COVID-19 therapies and may also explain the increased susceptibility to SARS-CoV-2 of autoimmune patients receiving therapies that impair the production of IgM.

Increased distension stimulates distal capillary growth as well as expression of specific angiogenesis genes in fetal mouse lungs

Abstract: Tracheal occlusion (TO) performed surgically in utero near the end of gestation causes a rapid increase in the distension of future airspaces, resulting in accelerated lung development. The authors hypothesize that TO stimulates microvascular growth concomitant with a rapid increase in the expression of genes implicated in angiogenesis. Mouse fetuses underwent in utero surgery (TO or sham-TO surgery) at 16.5 days of gestation, whereupon development was allowed to continue for a further 1 or 24 hours. Microvascular changes were assessed by immunohistochemical staining of fetal lung sections for platelet endothelial cell adhesion molecule-1. Levels of vascular endothelial growth factor-A (VEGF-A; isoforms 120, 164 and 188), VEGF receptors 1 and 2 (VEGFR-1 and -2), angiopoietins 1 and 2, and Tie2 mRNAs were determined by quantitative real-time polymerase chain reaction (PCR). The authors observed more intercapillary interconnection, less isolated capillaries, and a more extended capillary network inside septa of lungs that underwent 24 h of TO versus sham-TO. Moreover, the authors observed a significant increase in mRNA levels of VEGF 188 and VEGFR-1 as early as 1 hour following TO and of VEGFR-1 and angiopoietin 1 after 24 hours. Together, these results suggest that surgically applied stretching quickly enhances the expression of specific angiogenesis and vessel maintenance genes, which seems to result in the maturation and organization of a more extensive and complex capillary network.

Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

Abstract: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.

Guidelines for the use of flow cytometry and cell sorting in immunological studies

Abstract: The marriage between immunology and cytometry is one of the most stable and productive in the recent history of science. A rapid search in PubMed shows that, as of July 2017, using “flow cytometry immunology” as a search term yields more than 68 000 articles, the first of which, interestingly, is not about lymphocytes. It might be stated that, after a short engagement, the exchange of the wedding rings between immunology and cytometry officially occurred when the idea to link fluorochromes to monoclonal antibodies came about. After this, recognizing different types of cells became relatively easy and feasible not only by using a simple fluorescence microscope, but also by a complex and sometimes esoteric instrument, the flow cytometer that is able to count hundreds of cells in a single second, and can provide repetitive results in a tireless manner. Given this, the possibility to analyse immune phenotypes in a variety of clinical conditions has changed the use of the flow cytometer, which was incidentally invented in the late 1960s to measure cellular DNA by using intercalating dyes, such as ethidium bromide. The epidemics of HIV/AIDS in the 1980s then gave a dramatic impulse to the technology of counting specific cells, since it became clear that the quantification of the number of peripheral blood CD4+ T cells was crucial to follow the course of the infection, and eventually for monitoring the therapy. As a consequence, the development of flow cytometers that had to be easy-to-use in all clinical laboratories helped to widely disseminate this technology. Nowadays, it is rare to find an immunological paper or read a conference abstract in which the authors did not use flow cytometry as the main tool to dissect the immune system and identify its fine and complex functions. Of note, recent developments have created the sophisticated technology of mass cytometry, which is able to simultaneously identify dozens of molecules at the single cell level and allows us to better understand the complexity and beauty of the immune system.

Sex Differences and Sex Steroids in Lung Health and Disease

Abstract: Sex differences in the biology of different organ systems and the influence of sex hormones in modulating health and disease are increasingly relevant in clinical and research areas. Although work has focused on sex differences and sex hormones in cardiovascular, musculoskeletal, and neuronal systems, there is now increasing clinical evidence for sex differences in incidence, morbidity, and mortality of lung diseases including allergic diseases (such as asthma), chronic obstructive pulmonary disease, pulmonary fibrosis, lung cancer, as well as pulmonary hypertension. Whether such differences are inherent and/or whether sex steroids play a role in modulating these differences is currently under investigation. The purpose of this review is to define sex differences in lung structure/function under normal and specific disease states, with exploration of whether and how sex hormone signaling mechanisms may explain these clinical observations. Focusing on adult age groups, the review addresses the following: 1) inherent sex differences in lung anatomy and physiology; 2) the importance of certain time points in life such as puberty, pregnancy, menopause, and aging; 3) expression and signaling of sex steroid receptors under normal vs. disease states; 4) potential interplay between different sex steroids; 5) the question of whether sex steroids are beneficial or detrimental to the lung; and 6) the potential use of sex steroid signaling as biomarkers and therapeutic avenues in lung diseases. The importance of focusing on sex differences and sex steroids in the lung lies in the increasing incidence of lung diseases in women and the need to address lung diseases across the life span.

Fc glycans of therapeutic antibodies as critical quality attributes

Abstract: Critical quality attributes (CQA) are physical, chemical, biological or microbiological properties or characteristics that must be within an appropriate limit, range or distribution to ensure the desired product quality, safety and efficacy. For monoclonal antibody therapeutics that rely on fraction crystalizable (Fc)-mediated effector function for their clinical activity, the terminal sugars of Fc glycans have been shown to be critical for safety or efficacy. Different glycosylation variants have also been shown to influence the pharmacodynamic and pharmacokinetic behavior while other Fc glycan structural elements may be involved in adverse immune reactions. This review focuses on the role of Fc glycans as CQAs. Fc glycan information from the published literature is summarized and evaluated for impact on patient safety, immunogenicity, bioactivity and pharmacodynamics/pharmacokinetics.