Inhibition of CD147 Attenuates Stroke-Associated Pneumonia Through Modulating Lung Immune Response in Mice

Abstract

Background and Purpose: Acute ischemic stroke triggers a profound systemic and local immunodysfunction that increased the susceptibility to infections, especially stroke-associated pneumonia (SAP). Our previous study has shown that inhibition of CD147 ameliorates acute ischemic stroke, however, the role of CD147 in post-stroke lung infection has not been investigated. Methods: C57BL/6 mice were subjected to transient (60 min) middle cerebral artery occlusion, and treated with anti-CD147 antibody (αCD147). Lung histological changes, vascular permeability, and pulmonary edema were determined. Bacterial burden in the lung tissue and Broncho alveolar lavage fluid (BALF) were measured. Lung leukocyte infiltration, circulating platelet-leukocyte aggregates, cell type-specific IL-17A, and IFN-γ expression in the lung were detected by flow cytometry. Results: CD147 expression was markedly upregulated in the lung after stroke. αCD147 treatment significantly decreased the stroke-associated lung histological damages, bacterial load, vascular permeability and pulmonary edema. The protective effects by αCD147 treatment were associated with deceased lung inflammatory cell infiltration by reducing IL-17A expression in lung γδ T cells and attenuated bacterial load by enhancing IFN-γ expression in the lung NK1.1 + cells and CD4 + T cells. In addition, CD147 expression was also increased in the circulating platelets and leukocytes. Enhanced platelet-leukocyte aggregates following stroke was inhibited by αCD147 treatment. Conclusions: Inhibition of CD147 ameliorates aberrant lung inflammatory and immune response and reduces bacterial infection after stroke. CD147 might represent a novel and promising therapeutic target for post-stroke lung infection.

Peripheral inflammation and blood–brain barrier disruption: effects and mechanisms

“…For example, the adaptive immune system is activated following cerebral ischemia, and the peripheral immune cells, such as T cells and B cells, rapidly infiltrate the diseased brain and release various cytokines, including pro‐inflammatory cytokines (TNF‐α, IL‐1β, IL‐6) leading to blood vessels and BBB damage, and anti‐inflammatory cytokines (IL‐13, IL‐10, IL‐4, TGF‐β) extenuating the ischemic injury 40‐42 . Moreover, both immune cells and cytokines induce immunodepression after stroke, which leads to an increased incidence of infections such as pneumonia 43‐45 . It is not exactly clear whether BBB dysfunction induced by inflammation is the cause or complication of CNS disease, and further study to understand the role of peripheral inflammation on BBB function and the influence on CNS disease can provide a basis for clinical treatment of the disease to a certain extent.…”

Stroke-induced immunosuppression: implications for the prevention and prediction of post-stroke infections

“…The protein CD147 is expressed broadly in many leukocyte subtypes and is involved in some immune processes like T cell activation and Th17 cell differentiation. By inhibiting CD147, Jin et al [83] observed attenuation of lung damage, increased IFN-γ levels in the lungs, and the modulation of leukocyte subpopulation changes in the lungs of MCAO mice. Another immunomodulatory therapy involving the inhibition of PTEN seemed to reduce bacterial lung infections and mortality in MCAO possibly through the restoration of PI3K/Akt cascade in the lungs [84].…”

High Monocyte-To-Lymphocyte Ratio Is Associated With Stroke-Associated Pneumonia

“…Advanced age, male, stroke severity, dysphagia, and low estimated glomerular filtration rate (eGFR) are predictive factors for SAP ( 5 , 12 , 13 ). In an animal experiment, C57BL/6 mice treated with an anti-CD147 antibody could decrease the lung damages, bacterial load, and pulmonary edema after receiving middle cerebral artery occlusion ( 19 ).…”