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.
Highlights
Acute ischemic stroke produces local brain damage and triggers a profound systemic immune dysfunction, which results in approximately 30% of patients suffering from stroke-associated pneumonia (SAP) within the first few days after stroke [1,2,3]
Western blot analysis showed that Cluster of differentiation 147 (CD147) protein expression in the lung tissue was elevated significantly at 24 h, and continued to increase up to 72 h after stroke (The full images of western blot were available in Supplementary Figure 1) (Figure 1A)
The number of cells and levels of protein concentration in the Bronchoalveolar lavage fluid (BALF) were significantly increased after stroke, but these increases were inhibited in αCD147treated mice compared with isotype control group (Figure 1C)
Summary
Acute ischemic stroke produces local brain damage and triggers a profound systemic immune dysfunction, which results in approximately 30% of patients suffering from stroke-associated pneumonia (SAP) within the first few days after stroke [1,2,3]. Experimental studies have shown that prophylactic antibiotic treatment and/or inhibition of increased sympathetic activity using the β-adrenergic receptor blocker propranolol are effective for CD147 and Stroke-Associated Pneumonia preventing and treating SAP [4,5,6]. Two recent largescale clinical trials demonstrated that prophylactic antibiotic treatments did not reduce the incidence of mortality or SAP [7, 8]. 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, the role of CD147 in post-stroke lung infection has not been investigated
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