Smoking status and anti-inflammatory macrophages in bronchoalveolar lavage and induced sputum in COPD

<p>Abstract</p> <p>Background</p> <p>Macrophages have been implicated in the pathogenesis of COPD. M1 and M2 macrophages constitute subpopulations displaying pro- and anti-inflammatory properties. We hypothesized that smoking cessation affects macrophage heterogeneity in the lung of patients with COPD. Our aim was to study macrophage heterogeneity using the M2-marker CD163 and selected pro- and anti-inflammatory mediators in bronchoalveolar lavage (BAL) fluid and induced sputum from current smokers and ex-smokers with COPD.</p> <p>Methods</p> <p>114 COPD patients (72 current smokers; 42 ex-smokers, median smoking cessation 3.5 years) were studied cross-sectionally and underwent sputum induction (M/F 99/15, age 62 ± 8 [mean ± SD] years, 42 (31-55) [median (range)] packyears, post-bronchodilator FEV₁63 ± 9% predicted, no steroids past 6 months). BAL was collected from 71 patients. CD163⁺macrophages were quantified in BAL and sputum cytospins. Pro- and anti-inflammatory mediators were measured in BAL and sputum supernatants.</p> <p>Results</p> <p>Ex-smokers with COPD had a higher percentage, but lower number of CD163⁺macrophages in BAL than current smokers (83.5% and 68.0%, p = 0.04; 5.6 and 20.1 ×10⁴/ml, p = 0.001 respectively). The percentage CD163⁺M2 macrophages was higher in BAL compared to sputum (74.0% and 30.3%, p < 0.001). BAL M-CSF levels were higher in smokers than ex-smokers (571 pg/ml and 150 pg/ml, p = 0.001) and correlated with the number of CD163⁺BAL macrophages (Rs = 0.38, p = 0.003). No significant differences were found between smokers and ex-smokers in the levels of pro-inflammatory (IL-6 and IL-8), and anti-inflammatory (elafin, and Secretory Leukocyte Protease Inhibitor [SLPI]) mediators in BAL and sputum.</p> <p>Conclusions</p> <p>Our data suggest that smoking cessation partially changes the macrophage polarization <it>in vivo </it>in the periphery of the lung towards an anti-inflammatory phenotype, which is not accompanied by a decrease in inflammatory parameters.</p

Human Decidual Tissue Contains Disarmed CD8+Effector-memory T Cells

Transplantation and autoimmunit

Preeclampsia Is Characterized by Placental Complement Dysregulation

Immunopathology of vascular and renal diseases and of organ and celltransplantationIP1

Immunoregulation during human pregnancy

Transplantation and autoimmunit

Supplementary Material for: C-terminal PEGylation improves SAAP-148 peptide's immunomodulatory activities

Synthetic antibacterial and anti-biofilm peptide (SAAP)-148 was developed to combat bacterial infections not effectively treatable with current antibiotics. SAAP-148 is highly effective against antimicrobial-resistant (AMR) bacteria without inducing resistance, however challenges for further development of SAAP-148 include its cytotoxicity and short circulation half-life. To circumvent these drawbacks a library of SAAP-148 linked to polyethylene glycol (PEG) groups of various lengths was screened for in vitro antibacterial activity and hemolytic activity. Results indicated that PEGylated SAAP-148 variants combine antibacterial activities with reduced hemolysis compared to SAAP-148. Interestingly, pro-inflammatory immunomodulatory activities of SAAP-148 were enhanced upon C-terminal PEGylation, with SAAP-148-PEG27 showing most effect. SAAP-148-PEG27 enhanced SAAP-148’s capacity to chemoattract human neutrophils and was able to more efficiently (re)direct M-CSF-induced monocyte-macrophage differentiation towards type 1 macrophages compared to SAAP-148. Furthermore, dendritic cells with a stronger mature expression profile were produced if monocytes were exposed to SAAP-148-PEG27 during monocyte-immature dendritic cell differentiation in comparison to SAAP-148. Parameters that influenced the immunomodulatory activities of the peptide-PEG conjugate include i) the length of the PEG-group, ii) the position of PEG conjugation, and iii) the peptide sequence. Together, these results indicate that SAAP-148-PEG27 is highly effective in redirecting monocyte-macrophage differentiation towards a proinflammatory phenotype and promoting monocyte-mature dendritic cells development. Therefore, SAAP-148-PEG27 may be a promising agent to modulate inadequate immune responses in case of tumors and chronically infected wounds

Pregnancy-associated malaria affects toll-like receptor ligand-induced cytokine responses in cord blood.

Item does not contain fulltextBACKGROUND: Pregnancy-associated malaria is known to modify fetal immunity. Most previous studies have been cross-sectional in nature and have focused on the priming of acquired immune responses in utero. In this context, the influence of the timing and/or duration of placental infection with Plasmodium falciparum are unknown, and changes to innate immune responses have not been studied extensively. METHODS: Pregnant women in Gabon, where P. falciparum infection is endemic, were followed up through monthly clinical and parasitological examinations from the second trimester to delivery. Cells of neonates born to mothers who had acquired P. falciparum infection <or=1 month before delivery had significantly altered interferon-gamma and tumor necrosis factor-alpha responses after stimulation with the Toll-like receptor (TLR) ligands lipopolysaccharide and polyinosine-polycytidylic acid, compared with cells of neonates born either to mothers free of P. falciparum infection or to mothers who were successfully treated for malaria during pregnancy. An independent association between parity and neonatal TLR responsiveness was also discerned in our study. CONCLUSION: P. falciparum infection history during pregnancy appears to have a pronounced effect on neonatal innate immune responses. The observed effects may have profound implications for the outcome of newly encountered infections in early life

PRESENCE OF THE HLA-B27+/HLA-B*40:01+HIGH RISK ANKYLOSING SPONDYLITIS GENOTYPE IN EARLY BACK PAIN PATIENTS (RESULTS FROM THE DESIR AND SPACE COHORT)

Pathophysiology and treatment of rheumatic disease