Krzysztof Gomułka

Recent years have brought progress in understanding the role of the neutrophil, dispelling the dogma of homogeneous cells mainly involved in the prime defence against pathogens, shedding light on their pathogenic role in inflammatory diseases and on the importance of antineutrophil-cytoplasmic antibodies’ pathogenic role in ANCA-associated vasculitides vasculitis (AAV). Myeloperoxidase (MPO) and proteinase 3 (PR3) expressed in neutrophil granulocytes are the most common targets for ANCAs and contribute to the formation of MPO-ANCAs and PR3-ANCAs which, released to the bloodstream, become an excellent diagnostic tool for AAV. In this study, we focus on increasing the clinical and experimental evidence that supports the pathogenic role of ANCAs in AAV. Additionally, we discuss the diagnostic utility of ANCAs for disease activity and prognosis in AAV. Understanding the central role of ANCAs in AAV is crucial for advancing our knowledge of these complex disorders and developing targeted therapeutic strategies in the era of personalized medicine.

Asthma is a chronic, complex disease associated with heterogeneity in molecular pathways. Airway inflammation with different cell activation (e.g., eosinophils) and with hypersecretion of many cytokines (e.g., vascular endothelial growth factor—VEGF) might be relevant for asthma pathogenesis and responsible for airway hyperresponsiveness and remodeling. The aim of our study was to reveal the expression of activation marker CD11b on peripheral eosinophils unstimulated and after VEGF in vitro stimulation in asthmatics with different degrees of airway narrowing. The study population included a total of 118 adult subjects: 78 patients with asthma (among them 39 patients with irreversible bronchoconstriction and 39 patients with reversible bronchoconstriction according to the bronchodilation test) and 40 healthy participants as a control group. CD11b expression on peripheral blood eosinophils was detected in vitro using the flow cytometric method without exogenous stimulation (negative control), after N-formyl-methionine-leucyl-phenylalanine stimulation (fMLP; positive control) and after stimulation with VEGF in two concentrations (250 ng/mL and 500 ng/mL). CD11b marker was slightly presented on unstimulated eosinophils in asthmatics and the subgroup with irreversible airway narrowing (p = 0.06 and p = 0.07, respectively). Stimulation with VEGF enhanced the activity of peripheral eosinophils and induced CD11b expression in asthmatics in comparison with a healthy control (p < 0.05), but it was dependent neither on the concentration of VEGF nor on the degree of airways narrowing in patients with asthma. We present our findings to draw attention to the potential role of VEGF in the eosinophil priming and CD11b-mediated signaling in patients with asthma which is currently undervalued.