Increased CD11b and Decreased CD62L in Blood and Airway Neutrophils from Long-Term Smokers with and without COPD

Abstract

There is incomplete mechanistic understanding of the mobilization of neutrophils in the systemic and local compartment in smokers with chronic obstructive pulmonary disease (COPD). In this pilot study, we characterized how the adhesion molecules CD11b and CD62L, surface markers indicative of priming, are altered as neutrophils extravasate, and whether surface density of CD11b and CD62L differs between long-term tobacco smokers (LTS) with and without COPD compared with healthy never-smokers (HNS). Unstimulated blood neutrophils from LTS with (<i>n</i> = 5) and without (<i>n</i> = 9) COPD displayed lower surface density of CD62L compared with HNS (<i>n</i> = 8). In addition, surface density of CD11b was higher in bronchoalveolar lavage (BAL) neutrophils from LTS without COPD compared with those with COPD and HNS. Moreover, in BAL neutrophils from all study groups, CD62L was lower compared with matched blood neutrophils. In addition, BAL neutrophils responded with a further decrease in CD62L to ex vivo TNF stimulation. Thus, neutrophils in the airway lumen display a higher state of priming than systemic neutrophils and bear the potential to be further primed by local cytokines even with no smoking or the presence of COPD, findings that may represent a universal host defense mechanism against local bacteria. Moreover, systemic neutrophils are primed in LTS regardless of COPD. Further studies in larger materials are warranted to determine whether the priming of neutrophils is protective against COPD or merely preceding it.

Modelers Modelling Models

“…These findings led the authors to conclude that in amniotic fluids innate immune cells play an important role in cellular trafficking throughout the umbilical cord [1]. Their observations are in line with results showing that many immune cells have organ-specific and distinct functional populations and innate immune functions [2][3][4][5].…”

Tumor-Derived Factors Differentially Affect the Recruitment and Plasticity of Neutrophils

“…We next aimed to characterize the phenotypical and functional consequences of this plasticity in terms of surface marker expression, nuclear morphology, and neutrophilic functions in the newly formed LD-NDN, as compared to NDN and LDN. In order to assess whether this transition could be driven from a degranulation process, we first checked on NDN, LDN, and LD-NDN the surface expression of CD11b, as this integrin is known to be upregulated upon release of gelatinase granules and secretory vesicles from neutrophils [34,35]. We noted that, although all subpopulations expressed CD11b (Figure 5A, left panel), LD-NDN showed a strong increase in MFI compared to NDN and LDN (Figure 5A, central and right panels), supporting the hypothesis that NDN degranulation may lead to a density change.…”

Leptin Receptor q223r Polymorphism Influences Clostridioides difficile Infection-Induced Neutrophil CXCR2 Expression in an Interleukin-1β Dependent Manner

“…Integrins are hetero-dimers comprised of paired α and β chains that mediate leukocyte-endothelium interactions and participate in extravasation of neutrophils from blood vessels to inflamed tissue sites ( Zarbock et al, 2012 ). CD11b is a β2 integrin present on all neutrophils and its expression is upregulated during the innate host response to various noxious stimuli ( O’Hare et al, 2015 ; Hesselink et al, 2019 ; Stockfelt et al, 2020 ). CD11b dimerizes with CD18 (common α chain of various integrins) to promote neutrophil adhesion to endothelial cells and their trans-endothelial migration into tissue sites ( Zarbock and Stadtmann, 2012 ; Arnaout, 2016 ).…”