Increased CAP37 Expression in Stable Chronic Obstructive Pulmonary Disease

Objective Cationic antimicrobial protein of 37 kDa(CAP37),a neutrophil-derived protein originally identified for its antimicrobial activity,is now known to have many regulatory effects on host cells.However,its role in the pathogenesis of chronic obstructive pulmonary disease(COPD)has not been studied.We therefore investigated the expression of CAP37 in COPD and its effects on airway structural cells,including bronchial epithelial cells,smooth muscle cells,and fibroblasts.Methods CAP37 was detected in the lung tissue,sputum,and plasma of COPD patients and the control subjects,as well as in the neutrophils stimulated by cigarette smoke extract(CSE).BEAS-2B cells,human bronchial smooth muscle cells(HBSMCs),and MRC-5 cells were treated with CAP37 or an anti-CAP37 antibody plus CAP37.Interleukin(IL)-6 and IL-8 were detected in the BEAS-2B cells.The cell proliferation was analyzed in the HBSMCs.Collagens were also detected in the MRC-5 cells.Results The expression of CAP37 was increased in the lung tissue and sputum supernatant of the COPD patients compared with the control subjects.The sputum supernatant CAP37 levels were inversely correlated with the forced expiratory volume in the first second percentage predicted in COPD.CAP37 was induced by CSE stimulation in the peripheral blood neutrophils from healthy non-smokers.CAP37 induced expression of IL-6 and IL-8 in BEAS-2B cells,and collagen expression of lung fibroblasts(MRC-5 cells).However,CAP37 did not significantly alter the proliferation of the HBSMCs.Conclusion Our findings indicated that neutrophil-derived CAP37 may be involved in airway inflammation and fibrosis in COPD via affecting the bronchial epithelial cells,and fibroblasts,thus suggesting a possible role of CAP37 in the development and progression of COPD.

Cationic antimicrobial protein of Mr 37 kDa:a multifunctional inflammatory protein

PURPOSE: To investigate the role of cationic antimicrobial protein of Mr 37 kDa (CAP37) a neutrophil-derived inflammatory mediator on endothelial cell function. DATA SOURCES: Endothelial cells used in this study were obtained from human lung microvessels and rat aorta. The latter was a kind gift of Dr. Paula Grammas. The mono-mac 6 cell line used in this study was the generous gift of Dr. H.W. Loms Ziegler-Heitbrock. STUDY SELECTION AND DATA EXTRACTION: Endothelial cell proteins kinase C activity was determined by measuring calcium- and phospholipid-dependent phosphorylation of histone. Endothelial cell migration was determined using Costar Transwell apparatus. Cell surface expression of adhesion molecules, ICAM-1 and PECAM-1 was determined using flow cytometry. RT-PCR was used to amplify the CAP37 from endothelial cells treated with LPS. RESULTS: We demonstrated that CAP37 which was originally identified as having potent antimicrobial activity and chemotactic activity for monocytes was capable of modulating endothelial cell functions. CAP37 activated endothelial cell protein kinase C in a dose- and time-dependent fashion. Importantly CAP37 increased the adhesive properties of the endothelium for monocytes. CAP37 upregulated the well known adhesion molecules, ICAM-1 and PECAM-1 in a dose- and time-dependent manner. In addition, CAP37 promoted endothelial cell migration. Further investigations indicated that CAP37 was induced in endothelial cells in response to pro-inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-1 alpha as well as inflammatory mediators such as lipopolysaccharide. Unstimulated endothelial cells did not constitutively express CAP37. The cDNA sequence of endothelial CAP37 was determined and found to be highly homologous to the sequence obtained for neutrophil-derived CAP37. CONCLUSIONS: Our studies strongly suggest that CAP37 plays a pivotal role in monocyte-endothelial interactions and the transmigration of monocytes from the vasculature into extravascular tissues.

Rapid inactivation of multidrug-resistant bacteria and enhancement of osteoinduction via titania nanotubes grafted with polyguanidines

The rapid in situ inhibition of bacterial contamination and subsequent infection without inducing drug resistance is highly vital for the successful implantation and long-term service of titanium(Ti)-based orthopedic implants.However,the instability and potential cytotoxicity of current coatings have deterred their clinical practice.In this study,anodic oxidized titania nanotubes(TNT)were modified with antibacterial polyhexamethylene guanidine(PG)with the assistance of 3,4-dihydroxyphenylacetic acid.Interestingly,the prepared TNT-PG coating exhibited superior in vitro antibacterial activity than flat Ti-PG coating and effectively killed typical pathogens such as Escherichia coli and superbug methicillinresistant Staphylococcus aureus with above 4-log reduction(>99.99%killed)in only 5 min.TNT-PG coating also exerted excellent hemocompatibility with red blood cells and nontoxicity toward mouse pre-osteoblasts(MC3 T3-E1)in 1 week of coculture.In addition,the efficient in vivo anti-infective property of this coating was observed in a rat subcutaneous infection model.More importantly,TNT-PG coating improved the expression of alkaline phosphatase and enhanced the extracellular matrix mineralization of pre-osteoblasts,denoting its osteoinductive capacity.This versatile TNT-PG coating with excellent antibacterial activity and biocompatibility could be a promising candidate for advanced orthopedic implant applications.

Anti-lipopolysaccharide factor D from kuruma shrimp exhibits antiviral activity

Anti-lipopolysaccharide factors(ALFs)exhibit a potent antimicrobial activity against a broad range of bacteria,filamentous fungi,and viruses.In previous reports,seven groups of ALFs(groups A–G)were identified in penaeid shrimp.Among them,group D showed negative net charges and weak antimicrobial activity.Whether this group has antiviral function is not clear.In this study,the ALF sequences of penaeid shrimp were analyzed,and eight groups of ALF family(groups A–H)were identified.The four ALFs including MjALF-C2,MjALF-D1,MjALF-D2,and MjALF-E2 from kuruma shrimp Marsupenaeus japonicus were expressed recombinantly in Escherichia coli,and the antiviral activity was screened via injection of purified recombinant ALFs into shrimp following white spot syndrome virus(WSSV)infection.Results showed that the expression of Vp28(WSSV envelope protein)decreased significantly in the MjALF-D2-injected shrimp only.Therefore,MjALF-D2 was chosen for further study.Expression pattern analysis showed that MjAlf-D2 was upregulated in shrimp challenged by WSSV.The WSSV replication was detected in RNA,genomic DNA,and protein levels using VP28 and Ie1(immediate-early gene of WSSV)as indicators in MjALF-D2-injected shrimp following WSSV infection.Results showed that WSSV replication was significantly inhibited compared with that in the rTRX-or PBS-injected control groups.After knockdown of MjAlf-D2 in shrimp by RNA interference,the WSSV replication increased significantly in the shrimp.All these results suggested that MjALF-D2 has an antiviral function in shrimp immunity,and the recombinant ALF-D2 has a potential application for viral disease control in shrimp aquaculture.