Lack of CD34 produces defects in platelets, microparticles, and lung inflammation
- PDF / 17,626,088 Bytes
- 15 Pages / 595.276 x 790.866 pts Page_size
- 112 Downloads / 155 Views
REGULAR ARTICLE
Lack of CD34 produces defects in platelets, microparticles, and lung inflammation Gurpreet Kaur Aulakh 1 Received: 22 January 2020 / Accepted: 15 June 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Lung innate immune activation results in acute lung inflammation, which is characterized by alveolar barrier disruption and accumulation of cellular lung aggregates comprising neutrophils, platelets, mononuclear cells, and microparticles. CD34 is a sialomucin, with pan-selectin affinity and recently shown to protect the endothelial barrier in a bleomycin-induced lung injury model. However, there is very little information about the fundamental role of CD34 in regulation of the lung innate immune response. We hypothesized that CD34 regulates leukocyte recruitment by promoting optimal platelet activation (aggregation and spread) during bacterial lipopolysaccharide (LPS)-induced acute lung injury. Therefore, we utilized CD34 knock-out (KO) and wild-type (WT) mice to analyze and compare the morphology and expression of leukocyte subsets from the pulmonary and systemic compartments. We utilized the chemotactic N-formylated tri-peptide, fMLP, to understand platelet aggregation in vitro, and the fundamental immune stimulant, LPS, to induce lung injury and understand platelet activation ex vivo. Our data reveal that under steady-state conditions, KO mice possess large aggregates of integrin β3 (CD61)-positive microparticles in peripheral blood. Moreover, the KO mice recruit a large number of neutrophils to lungs, which are not cleared even at 36-h post-LPS exposure. The KO mice display an increased platelet CD61 expression, which aggregates, but does not spread normally in response to in vitro fMLP treatment. The KO platelets display similar deficits in their spreading ability even after ex vivo LPS exposure. Thus, our data demonstrate that CD34 modulates platelet biology, microparticle aggregation, and neutrophil recruitment during murine lung inflammation. Keywords CD34 . Lung inflammation . Neutrophil . Platelets . Microparticles
Introduction Alveolar barrier disruption and cellular lung aggregates comprising neutrophils, platelets, mononuclear cells, and microparticles are hallmarks of the ensuing lung damage due to innate immune activation (Aras et al. 2004). The resulting alveolar and interstitial edema, alveolar hemorrhage, and interstitial accumulation of red blood cells (RBCs) are central features of the early phases of acute lung injury (ALI) and its pathologic correlate, diffuse alveolar damage, which, if not corrected, can compromise lung function and disseminate to multiple organs (Matsumoto et al. 2015; Middleton et al. 2016, 2018). * Gurpreet Kaur Aulakh [email protected] 1
Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Canada
Platelet shape change and activation mediate leukocyte activation and aggregation (Grommes et al. 2012) and influence escape of RBCs from microvessels, in addition to regul
Data Loading...
