Interleukin-2 (IL-2) is an essential growth factor for T cells. Previous studies have shown that human peripheral eosinophils respond to IL-2 in chemotaxis and express the IL-2 receptor (CD25). In addition, eosinophils have been shown to transcribe messenger RNA for IL-2. The aim of the present study was to determine whether eosinophils translate mRNA for IL-2 and to determine the site of intracellular localization. By immunocytochemistry, an average of 9% of cells showed cytoplasmic staining for IL-2 in freshly isolated unstimulated blood eosinophils obtained from asthmatic subjects who were not receiving oral corticosteroid treatment (n = 5). Freshly isolated, disrupted, highly purified eosinophils (> 99%, by CD16- immunomagnetic selection) contained an average of 6 pg/10(6) cells of IL-2 measured by a specific enzyme linked immunosorbent assay (ELISA) (n = 7). Purified eosinophil incubated with serum-coated Sephadex beads showed an increase in the amount of intracellularly-retained IL-2 (26.2 +/- 7.2 pg/10(6) cells) with some evidence for release of this cytokine but only in three out of six eosinophil preparations (range 1.3-5.8 pg/10(6) cells). The intracellular localization of IL-2 was determined by fractionation of the cells on a linear (0-45%) Nycodenz gradient in sucrose buffer followed by detection of IL-2 in the fractions using an IL-2-specific ELISA and dot blotting. The majority of the IL-2 detected co-eluted with known eosinophil granule markers (i.e. major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO) and beta-hexosaminidase) but small quantities were also detected in the cytosolic (lactate dehydrogenase-(LDH) associated) and membrane (CD9+) fractions. Immunogold labelling of intact eosinophils using an anti-IL-2 monoclonal antibody confirmed IL-2 immunoreactivity in association with the eosinophil crystalline granule cores. These data are consistent with the hypothesis that eosinophils synthesize, release and store IL-2 largely within cystalloid granules. This stored IL-2 may serve as a reservoir for rapid release of IL-2 in inflammatory reactions associated with eosinophilia.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1383982 | PMC |
Front Immunol
January 2025
Guangdong Immune Cell Therapy Engineering and Technology Research Center, Center for Protein and Cell-based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Chimeric antigen receptor T-cell (CAR-T) therapies have shown promise in glioblastoma clinical studies, but responses remain inconsistent due to heterogeneous tumor antigen expression and immune evasion post-treatment. NKG2D CAR-T cells have demonstrated a favorable safety profile in patients with hematologic tumors, and showed robust antitumor efficacy in various xenograft models, including glioblastoma. However, malignant glioma cells evade immunological surveillance by reducing NKG2D ligands expression or cleavage.
View Article and Find Full Text PDFPhysiol Behav
January 2025
Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China. Electronic address:
Background: Continuous electroacupuncture pre-conditioning (EPRC) and post-conditioning (EPOC) effectively improve motor dysfunction after acute cerebral ischemia, but they require multiple treatments. Recently, electroacupuncture per-conditioning (EPEC) has demonstrated neuroprotective effects, indicating that this single-session intervention has short-term efficacy.
Objective: To evaluate the effect of EPEC at Huantiao (GB30) on motor recovery in acute cerebral ischemia mice.
Cytokine
January 2025
Multidisciplinary Health Institute, Federal University of Bahia, Vitória da Conquista 45029-094, Bahia, Brazil. Electronic address:
Background: Understanding the immunopathogenesis of COVID-19 has yielded valuable insights into predicting adverse outcomes-particularly mortality. However, significant gaps persist in our comprehension of the complex interplay among the proposed pathophysiological mechanisms. Here, we aim to investigate the immunological factors associated with mortality in critically ill, unvaccinated COVID-19 patients admitted to the intensive care unit (ICU).
View Article and Find Full Text PDFBioorg Med Chem
January 2025
Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, #555 Zu Chong Zhi Road, Shanghai 201203 China; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Qixia District, Nanjing 210023 China; School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024 China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:
Hematopoietic progenitor kinase 1 (HPK1) has emerged as a promising target for cancer immunotherapy due to its critical role as a negative regulator of T cell receptor (TCR) signaling. Despite this potential, no HPK1 inhibitors have been approved for cancer treatment, underscoring the need for structurally novel inhibitors. Herein, we describe the design, synthesis and biological evaluation of a series of potent HPK1 inhibitors based on our previously identified hit 9.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!