Acute lung injury (ALI) is characterized by pulmonary diffusion abnormalities that may progress to multiple-organ failure in severe cases. There are limited effective treatments for ALI, which makes the search for new therapeutic avenues critically important. Macrophages play a pivotal role in the pathogenesis of ALI. The degree of macrophage polarization is closely related to the severity and prognosis of ALI, and S100A9 promotes M1 polarization of macrophages. The present study assessed the effects of S100A9-gene deficiency on macrophage polarization and acute lung injury. Our cohort study showed that plasma S100A8/A9 levels had significant diagnostic value for pediatric pneumonia and primarily correlated with monocyte-macrophages and neutrophils. We established a lipopolysaccharide (LPS)-induced mouse model of acute lung injury and demonstrated that knockout of the S100A9 gene mitigated inflammation by suppressing the secretion of pro-inflammatory cytokines, reducing the number of inflammatory cells in the bronchoalveolar lavage fluid, and inhibiting cell apoptosis, which ameliorated acute lung injury in mice. The in vitro and in vivo mechanistic studies demonstrated that S100A9-gene deficiency inhibited macrophage M1 polarization and reduced the levels of pulmonary macrophage chemotactic factors and inflammatory cytokines by suppressing the TLR4/MyD88/NF-κB signaling pathway and reversing the expression of the NLRP3 pyroptosis pathway, which reduced cell death. In conclusion, S100A9-gene deficiency alleviated LPS-induced acute lung injury by inhibiting macrophage M1 polarization and pyroptosis via the TLR4/MyD88/NFκB pathway, which suggests a potential therapeutic strategy for the treatment of ALI.

Mycoplasma pneumoniae-induced pneumonia (MPP) is a common cause of community-acquired respiratory tract infections, increasing risk of morbidity and mortality, in children. However, diagnosing early-stage MPP is difficult owing to the lack of good diagnostic methods. Here, we examined the protein profile of bronchoalveolar lavage fluid (BALF) and found that S100A8/A9 was highly expressed. Enzyme-linked immunosorbent assays used to assess protein levels in serum samples indicated that S100A8/A9 concentrations were also increased in serum obtained from children with MPP, with no change in S100A8/A9 levels in children with viral or bacterial pneumonia. In vitro, S100A8/A9 treatment significantly increased apoptosis in a human alveolar basal epithelial cell line (A549 cells). Bioinformatics analyses indicated that up-regulated S100A8/A9 proteins participated in the interleukin (IL)-17 signaling pathway. The origin of the increased S100A8/A9 was investigated in A549 cells and in neutrophils obtained from children with MPP. Treatment of neutrophils, but not of A549 cells, with IL-17A released S100A8/A9 into the culture medium. In summary, we demonstrated that S100A8/A9, possibly released from neutrophils, is a new potential biomarker for the clinical diagnosis of children MPP and involved in the development of this disease through enhancing apoptosis of alveolar basal epithelial cells.

Background: Mycoplasma pneumoniae pneumonia (MPP) is common among children, but the impact of atopy on MPP severity in children is unknown. This study investigated whether atopic vs. nonatopic children had greater MPP severity.Methods: Retrospective analysis was conducted on 539 (ages 3–14 years) patients who were hospitalized in the First Affiliated Hospital of Anhui Medical University for MPP between January 2018 and December 2021, 195 were atopic and 344 were nonatopic. Of them, 204 had refractory MPP, and 335 had general MPP. And of atopic children, 94 had refractory MPP, and 101 had general MPP. Data on demographic and clinical characteristics, laboratory findings, clinical treatments were analyzed.Results: Significantly more boys with MPP were atopic than nonatopic (P < 0.05). More atopic (than nonatopic) children presented with prolonged fever and hospitalization, severe extra-pulmonary complications, asthma attaking, steroid and oxygen treatment, and increased IgE levels (all P < 0.05). In atopic (vs. nonatopic) children with MPP, the incidence of sputum plugs under the fiberoptic bronchoscopy and lobar pneumonia was significantly increased and required bronchoscopy-assisted and steroid therapy. Compared with nonatopic children, more atopic children developed refractory MPP (P < 0.05). Prolonged fever and hospitalization, severe extra-pulmonary complications, lymphocyte count, procalcitonin and lactate dehydrogenase levels, and percentages of atopy were all significantly higher (P < 0.05) among children with refractory MPP vs. general MPP. Moreover, Prolonged fever and hospitalization, lymphocyte count, procalcitonin and lactate dehydrogenase levels, and the treantment of steroid were all significantly higher (P < 0.05) among atopic children with refractory MPP vs. general MPP. Spearman correlation analysis showed strong associations between atopy and male sex, length of hospital stay, fever duration, IgE level, wheezing, lobar pneumonia, refractory MPP, and treatment with oxygen, hormones or bronchoscopy (P < 0.05).Conclusions: Atopy may be a risk factor for and was positively correlated with the severity of MPP in children.