Olivia Tellez-Jimenez, Christian Trejo-Jasso, Patricia Ramos-Ramirez, Maryana Tinoco-Cuellar, Diana García-Trejo, Angélica Flores-Flores, Rocío Chapela, José Luis Miguel-Reyes, Blanca Bazán-Perkins
<p>To the Editor,</p><p>Integrins are ubiquitous transmembrane glycoprotein receptors involved in bidirectional signaling across the cell membrane. Integrins are composed of a noncovalent complex that contains an α-subunit and a β-subunit, with 18 and 8 variations, respectively, forming a total of 24 distinct heterodimer.<span><sup>1</sup></span> The integrin β1 subunit can interact with 12 α subunits, from α1 to α11 and αv. β2 integrins, along with α4β1, are cell adhesion ligands of leukocyte receptors.<span><sup>2</sup></span> In asthma model, various polypeptides containing both cytosolic and extracellular β1 integrin subunits were detected in airway myocytes and connective tissue, suggesting the secretion of the β1 integrin subunit.<span><sup>3</sup></span> In the context of asthma patients, studies have documented the presence of soluble extracellular domain of α1 and α2 integrin subunits in serum.<span><sup>4</sup></span> However, it remains unclear whether cytosolic integrins domains are present in fluids, such as serum, within the context of the asthma.</p><p>In patients with asthma (Supporting Information S1: Table S1), the levels of the extracellular domain of α1 and β1 integrin subunits, as well as the intracellular domain of α1 and β2 integrin subunits, were similar to those of healthy subjects (Figure 1). However, in asthma patients, the levels of the extracellular domain of α2 and β2 integrin subunits, as well as the intracellular domain of α2 and β1 integrin, were higher than those observed in healthy subjects (<i>n</i> = 23, <i>p</i> < 0.0001). This data is consistent with observations in persistent asthma patients, where an increase in serum soluble α2 integrin (extracellular domain) was observed compared to non-persistent asthma patients, while α1 integrin remained unchanged.<span><sup>4</sup></span> Interestingly, the expression patterns of integrin β1, α1, and α2 subunits in asthma differed from those observed in scleroderma patients (Supporting Information S1: Figure S1). The integrins α1β1 and α2β1 act as receptors for various types of collagens (I, III, IV, and XIII), each with distinct functions.<span><sup>5</sup></span> Additionally, integrin fragments have the ability to form heterodimers while retaining identical antigenic and ligand-binding properties as the complete transmembrane integrin.<span><sup>6</sup></span> Therefore, the presence of functional soluble integrin heterodimers in serum is feasible.</p><p>The changes in the expression of the β1 integrin intracellular domain and both domains of the α2 integrin inversely correlate with FEV1 (Table 1), implying that the severity of asthma may be associated with an upregulation of these integrins. Conversely, the β2 integrin extracellular domain exhibited a direct correlation with FEV1. Supporting this finding, a recent study demonstrated that in asthma patients, this integrin subunit is predominantly released by metalloproteinase-9 (MMP-9) during asthma exacerbatio
{"title":"Identifying integrins secreted in serum: Unveiling their correlation with inflammation and asthma—A preliminary study","authors":"Olivia Tellez-Jimenez, Christian Trejo-Jasso, Patricia Ramos-Ramirez, Maryana Tinoco-Cuellar, Diana García-Trejo, Angélica Flores-Flores, Rocío Chapela, José Luis Miguel-Reyes, Blanca Bazán-Perkins","doi":"10.1002/clt2.70023","DOIUrl":"10.1002/clt2.70023","url":null,"abstract":"<p>To the Editor,</p><p>Integrins are ubiquitous transmembrane glycoprotein receptors involved in bidirectional signaling across the cell membrane. Integrins are composed of a noncovalent complex that contains an α-subunit and a β-subunit, with 18 and 8 variations, respectively, forming a total of 24 distinct heterodimer.<span><sup>1</sup></span> The integrin β1 subunit can interact with 12 α subunits, from α1 to α11 and αv. β2 integrins, along with α4β1, are cell adhesion ligands of leukocyte receptors.<span><sup>2</sup></span> In asthma model, various polypeptides containing both cytosolic and extracellular β1 integrin subunits were detected in airway myocytes and connective tissue, suggesting the secretion of the β1 integrin subunit.<span><sup>3</sup></span> In the context of asthma patients, studies have documented the presence of soluble extracellular domain of α1 and α2 integrin subunits in serum.<span><sup>4</sup></span> However, it remains unclear whether cytosolic integrins domains are present in fluids, such as serum, within the context of the asthma.</p><p>In patients with asthma (Supporting Information S1: Table S1), the levels of the extracellular domain of α1 and β1 integrin subunits, as well as the intracellular domain of α1 and β2 integrin subunits, were similar to those of healthy subjects (Figure 1). However, in asthma patients, the levels of the extracellular domain of α2 and β2 integrin subunits, as well as the intracellular domain of α2 and β1 integrin, were higher than those observed in healthy subjects (<i>n</i> = 23, <i>p</i> < 0.0001). This data is consistent with observations in persistent asthma patients, where an increase in serum soluble α2 integrin (extracellular domain) was observed compared to non-persistent asthma patients, while α1 integrin remained unchanged.<span><sup>4</sup></span> Interestingly, the expression patterns of integrin β1, α1, and α2 subunits in asthma differed from those observed in scleroderma patients (Supporting Information S1: Figure S1). The integrins α1β1 and α2β1 act as receptors for various types of collagens (I, III, IV, and XIII), each with distinct functions.<span><sup>5</sup></span> Additionally, integrin fragments have the ability to form heterodimers while retaining identical antigenic and ligand-binding properties as the complete transmembrane integrin.<span><sup>6</sup></span> Therefore, the presence of functional soluble integrin heterodimers in serum is feasible.</p><p>The changes in the expression of the β1 integrin intracellular domain and both domains of the α2 integrin inversely correlate with FEV1 (Table 1), implying that the severity of asthma may be associated with an upregulation of these integrins. Conversely, the β2 integrin extracellular domain exhibited a direct correlation with FEV1. Supporting this finding, a recent study demonstrated that in asthma patients, this integrin subunit is predominantly released by metalloproteinase-9 (MMP-9) during asthma exacerbatio","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 2","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}