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[Display omitted] • Macrophage-specific SAP is the main source of the elevated level of periodontal SAP during periodontitis. • SAP deficiency exacerbated periodontitis, inflammation, and infiltration of M1-type proinflammatory macrophages in the periodontium. • SAP deficiency resulted in a higher abundance of Porphyromonas genus in the oral cavity of periodontitis mice. • SAP depleted macrophages induced C5a release from P. gingivalis and inhibited macrophage phagocytosis of P. gingivalis via C5a-C5aR signaling. • A higher abundance of Porphyromonas during SAP deficiency could promote M1 macrophage polarization and inflammation in the periodontium. Serum amyloid P component (SAP) regulates the innate immune system and microbial diseases. Periodontitis is an inflammatory oral disease developed by the host immune system's interaction with the dysbiotic oral microbiome, thereby SAP could play a role in periodontitis pathogenicity. To investigate the role of SAP in oral microbiome modulation and peridontitis pathogenicity. In this study, wildtype and SAP-knockout (KO) mice were used. Ligature-based periodontitis was developed in mice. Oral microbiome diversity was analyzed by 16 s rRNA sequencing. Macrophages and Porphyromonas gingivalis (P. gingivalis) co-culture system analyzed the effect of SAP in macrophage phagocytosis of P. gingivalis. The level of SAP was upregulated in the periodontitis-affected periodontium of humans and mice but not in the liver and blood circulation. Periodontal macrophages were the key source of upregulated SAP in periodontitis. SAP-KO aggravated periodontal inflammation, periodontitis, and a higher number of M1-type inflammatory macrophage infiltration in the periodontium. The oral microbiome of SAP-KO periodontitis mice was altered with a higher abundance of Porphyromonas at the genus level. SAP-KO macrophages showed compromised phagocytosis of P. gingivalis in the co-culture system. Co-culture of SAP-KO macrophages and P. gingivalis induced the C5a expression and exogenous SAP treatment nullified this effect. Exogenous recombinant SAP treatment did not affect P. gingivalis growth and opsonization. PMX205, an antagonist of C5a, treatment robustly enhanced P. gingivalis phagocytosis by SAP-KO macrophages, indicating the involvement of the C5a-C5aR signaling in the compromised P. gingivalis phagocytosis by SAP-KO macrophages. SAP deficiency aggravates periodontitis possibly via C5a-C5aR signaling-mediated defective macrophage phagocytosis of P. gingivalis. A higher abundance of P. gingivalis during SAP deficiency could promote M1 macrophage polarization and periodontitis. This finding suggests the possible protecting role of elevated levels of periodontal SAP against periodontitis progression. [ABSTRACT FROM AUTHOR]

• TREM-1 expression was increased in ExoCSE compared to ExoPBS. • ExoCSE promoted M1 macrophage polarization by upregulating TREM-1 expression. • ExoCSE aggravated the CS-induced lung injury in COPD mice. Chronic obstructive pulmonary disease (COPD) is a persistent respiratory disorder that is primarily caused by exposure to cigarette smoke (CS). Exosomes have emerged as crucial mediators of intercellular communication, but their role in CS-induced COPD is not fully understood. Here, we investigated whether exosomes derived from cigarette smoke extract (CSE)-treated mouse airway epithelial cells (MAECs) promote M1 macrophage polarization by upregulating triggering receptor expressed on myeloid cells-1 (TREM-1) expression during COPD pathogenesis. The exosomes isolated from PBS- or CSE-treated MAECs were named as ExoPBS or ExoCSE, respectively. Macrophages were transfected with si-TREM-1 to explore the role of TREM-1 in ExoCSE-induced M1 macrophage polarization. The lentivirus expressing shTREM-1 was injected into COPD model mice by intranasal instillation, which was carried out to explore the in vivo role of TREM-1 in ExoCSE-induced M1 macrophage polarization and CS-induced lung injury. We isolated ExoPBS and ExoCSE successfully, and found that ExoCSE promoted M1 macrophage polarization. Furthermore, we found that the promotion of ExoCSE to M1 macrophage polarization was partly reversed by TREM-1 knockdown. The results of animal experiments showed that ExoCSE administration aggravated CS-induced impairment in pulmonary function, lung injury and M1 macrophage polarization, which were partly rescued by TREM-1 silencing. Overall, ExoCSE promoted M1 macrophage polarization by upregulating TREM-1 expression, thereby aggravating the development of COPD. [ABSTRACT FROM AUTHOR]

Objective Serum amyloid P conpoent (SAP), a member of the pentraxin family, interact with pathogens and cell debris to promote their removal by macrophages and neutrophils and is co-localized with atherosclerotic plaques in patients. However, the exact mechanism of SAP in atherogenesis is still unclear. We investigated whether SAP influence macrophage recruitment and foam cell formation and ultimately affect atherosclerotic progression. Methods we generated apoE −/− ; SAP −/− (DKO) mice and fed them western diet for 4 and 8 weeks to characterize atherosclerosis development. Results SAP deficiency effectively reduced plaque size both in the aorta (p = 0.0006 for 4 wks; p = 0.0001 for 8 wks) and the aortic root (p = 0.0061 for 4 wks; p = 0.0079 for 8wks) compared with apoE −/− mice. Meanwhile, SAP deficiency inhibited oxLDL-induced foam cell formation (p = 0.0004) compared with apoE −/− mice and SAP treatment increases oxLDL-induced foam cell formation (p = 0.002) in RAW cells. Besides, SAP deficiency reduced macrophages recruitment (p = 0.035) in vivo and in vitro (p = 0.026). Furthermore, SAP treatment enhanced CD36 (p = 0.007) and FcγRI (p = 0.031) expression induced by oxLDL through upregulating JNK and p38 MAPK phosphorylation whereas specific JNK1/2 inhibitor reduced CD36 (p = 0.0005) and FcγRI (P = 0.0007) expression in RAW cell. SAP deficiency also significantly decreased the expression of M1 and M2 macrophage markers and inflammatory cytokines in oxLDL-induced macrophages. Conclusion SAP deficiency mitigated foam cell formation and atherosclerotic development in apoE −/− mice, due to reduction in macrophages recruitment, polarization and pro-inflammatory cytokines and inhibition the CD36/FcγR-dependent signaling pathway. [ABSTRACT FROM AUTHOR]