Rat anti-Mouse CD68 Monoclonal antibody, clone GB-22

Neuroinflammation contributes to the pathogenesis of early brain injury induced by subarachnoid hemorrhage (SAH). Previous reports have demonstrated that triggering receptor expressed on myeloid cells 1 (TREM-1) regulates inflammatory response caused by ischemic stroke or myocardial infarction. However, whether TREM-1 could modulate neuroinflammation after SAH remains largely unknown. Here, using a mouse model of SAH, we found that the expression of TREM-1 was mainly located in microglia cells and increased to peak at 24 h following SAH. Then, TREM-1 antagonist or mimic was intranasally administrated to investigate its effect on SAH. TREM-1 inhibition with LP17 improved neurological deficits, mitigated brain water content, and preserved brain-blood barrier integrity 24 h after SAH, whereas recombinant TREM-1, a mimic of TREM-1, deteriorated these outcomes. In addition, LP17 administration restored long-term sensorimotor coordination and cognitive deficits. Pharmacological blockade of TREM-1 reduced TUNEL-positive and FJC-positive neurons, and CD68-stained microglia in ipsilateral cerebral cortex. Neutrophil invasion was inhibited as protein level of myeloperoxidase (MPO), and MPO-positive cells were both decreased. Moreover, we found that LP17 treatment ameliorated microglial pyroptosis by diminishing levels of N-terminal fragment of GSDMD (GSDMD-N) and IL-1 beta production. Mechanistically, both in vivo and in vitro, we depicted that TREM-1 can trigger microglial pyroptosis via activating NLRP3 inflammasome. In conclusion, our results revealed the critical role of TREM-1 in neuroinflammation following SAH, suggesting that TREM-1 inhibition might be a potential therapeutic approach for SAH.

Background. Macrophages are important immune cells involved in Mycobacterium tuberculosis (M.tb) infection. To further investigate the degree of disease development in patients with spinal tuberculosis (TB), we conducted research on macrophage polarization. Methods. Thirty-six patients with spinal TB and twenty-five healthy controls were enrolled in this study. The specific morphology of tuberculous granuloma in spinal tissue was observed by hematoxylin-eosin (H&E) staining. The presence and distribution of bacilli were observed by Ziehl-Neelsen (ZN) staining. Macrophage-specific molecule CD68 was detected by immunohistochemistry (IHC). M1 macrophages play a proinflammatory role, including the specific molecule nitric oxide synthase (iNOS) and the related cytokine tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). M2 macrophages exert anti-inflammatory effects, including the specific molecule CD163 and related cytokine interleukin-10 (IL-10). The above markers were all detected by quantitative real-time PCR (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and IHC. Results. Typical tuberculous granuloma was observed in the HE staining of patients with spinal TB. ZN staining showed positive expression of Ag85B around the caseous necrosis tissue and Langerhans multinucleated giant cells. At the same time, IHC results indicated that CD68, iNOS, CD163, IL-10, TNF-alpha, and IFN-gamma were expressed around the tuberculous granuloma, and their levels were obviously higher in close tissue than in the distant tissue. RT-PCR and ELISA results indicated that IL-10, TNF-alpha, and IFN-gamma levels of TB patients were also higher than those of the healthy controls. Conclusion. The report here highlights that two types of macrophage polarization (M1 and M2) are present in the tissues and peripheral blood of patients with spinal TB. Macrophages also play proinflammatory and anti-inflammatory roles. Macrophage polarization is involved in spinal TB infection.