胎儿骨的生物学特性及其应用

临床上许多骨科医师乐意采用自体骨移植来治疗因创伤和骨病所致的骨缺损。自体植骨的骨生成能力强,容易与骨融合,但患者要承受切口增多、手术麻醉时间长、伤口出血感染等风险,以及因牺牲正常结构而使供骨部的稳定性减弱等不足。自１９１８年Ｃａｌｉｅ首先报道采用同种...     

干细胞因子的研究及其应用

人干细胞因子（hSCF)是新近发现的重要造血细胞因子，它是酪氨酸激酶受体c-Kit的配体。SCF主要作用于早期造血干细胞、原始造血祖细胞，并且诱导这些细胞的存活、增殖和分化。SCF单独使用生物学作用低，但它与其它细胞因子具有强的协同作用。在临床I、Ⅱ和Ⅲ期研究中，SCF和G－CSF联合应用，与单独使用G－CSF比较，CD34^ 细胞数增加2－3倍。安进公司采用基因重组技术在大肠杆菌中生产的重组人SCF（r-met hSCF)商品名为STEMGENTM。SCF临床使用，包括体内干细胞扩增治疗（ex vivo)和用于基因治疗的体外培养造血干细胞。SCF与G－CSF联合使用刺激扩增外周血干／祖细胞（PBPC），可用于干／祖细胞移植，以增加患者所需PBPC的比例，减少收集PBPC的次数。本综述主要介绍了人SCF的功能，临床研究和其它潜在应用。     

蛋氨酸脑啡肽研究进展及其应用前景

由于蛋氨酸脑啡肽联系着神经、免疫两大系统,具有独特的生物学活性,多年来一直受到广泛重视.目前,蛋氨酸脑啡肽应用于免疫相关疾病治疗的研究已经取得显著进展.本文综述了蛋氨酸脑啡肽的生物学功能的研究进展及其作用机制,并展望了其应用于癌症、艾滋病等重大免疫相关疾病的广阔前景.     

vIL—10的生物学特性及其应用研究进展

ｖＩＬ－１０是ＥＢＶ（ＥＢ）病毒产生的,具有细胞因子ＩＬ－１０许多类似的生物活性,但对某些细胞如鼠胸腺细胞及Ｔ细胞的作用又不同于ＩＬ－１０。由于其免疫抑制特性,在器官移植中其基因被转移移植进行抗排斥的研究。本文就ｖＩＬ－１０的产生、生物学特性及结构和功能的关系及在器官移植中的应用进行了简要综述。     

蛋氨酸脑啡肽研究进展及其应用前景

由于蛋氨酸脑啡肽联系着神经、免疫两大系统,具有独特的生物学活性,多年来一直受到广泛重视。目前,蛋氨酸脑啡肽应用于免疫相关疾病治疗的研究已经取得显著进展。本文综述了蛋氨酸脑啡肽的生物学功能的研究进展及其作用机制,并展望了其应用于癌症、艾滋病等重大免疫相关疾病的广阔前景。     

白细胞介素-4生物学功能及其临床应用

白细胞介素-4(interleukin-4,IL-4)是20世纪80年代初发现的, 具有多种生物功能的一种细胞因子.IL-4又名B细胞生长因子(B cell growth factor, BCGF), B细胞分化因子r(B cell differentiating factor r, BCDF), B细胞刺激因子-1(B cell stimulating factor-1, BSF-1), T细胞生长因子-Ⅱ(T cell growth factor Ⅱ, TCGF-Ⅱ)和肥大细胞生长因子-Ⅱ(mast cell growth factor Ⅱ, MCGF-Ⅱ).1986年其基因克隆成功, 国际统一命名为IL-4.     

酸性成纤维细胞生长因子生物学特性及其应用研究进展

1974年,Gospodarowicz等从牛脑垂体中分离纯化出一种对成纤维细胞系Balb/c3T3的分裂增生具有促进效应的多肽,命名为成纤维细胞生长因子,其等电点为9．16。后来发现脑组织中尚有另外一种与其同源性较强、功能相似但等电点为5．16的FGF,     

不同转移特性瘤细胞系的筛选及其生物学特性

目的：探讨与肿瘤转移相关的某些生物学特性。方法：将小鼠乳腺癌Ｃａ７６１－ＦＰ８／Ｌ和Ｃａ７６１－ＦＬ１０／Ｌ经体内筛选得到细胞系Ｃａ７６１－Ｐ５Ｂ和Ｃａ７６１＝Ｌ６Ｂ，并观察其瘤细胞与凝集反应、靶器官组织条件培养基对瘤细胞真挚化作用等，结果：Ｃａ７６１－Ｐ５Ｂ具有高肺转移、低淋巴结转移特性，Ｃａ７６１－Ｌ５Ｂ具有低肺、低淋巴结转移特性。两个瘤细胞系的细胞表面的糖基表达，对条件培养的趋化反应不同。结     

KGF-2的性质及其在基因美容中的应用

角质细胞生长因子-2(Keratinocyte growth factor-2,KGF-2)是具有肝素结合特性的成纤维细胞生长因子(FGFs)超家族中角质细胞生长因子家族的一员,由成纤维细胞及其他间质细胞分泌,成熟KGF-2为169个氨基酸残基的单链多肽,分子量为19.3～24KD.与其他FGF不同,KGF-2能特异性促进上皮细胞的增殖、分化和迁移,这是由于KGF受体主要存在于上皮细胞的缘故.目前证实,KGF-2在胚胎发育、血管生成、损伤修复、促毛发生长等生理和病理过程中起着显著的作用.本文着重展望了角质细胞生长因子-2在基因美容中的发展前景.     

HuGM-CSF的生物学功能及临床应用

人粒细胞 巨噬细胞集落刺激因子 (HuGM CSF)是一种能促进骨髓粒系、单核细胞系、巨噬细胞系分化和成熟 ,并增强其成熟细胞功能的多效应细胞因子。DNA重组技术的发展 ,使得利用基因工程方法大量生产细胞因子成为可能。近年来 ,随着对GM CSF研究的不断深入 ,认识也日趋成熟 ,临床应用则非常广泛。本文将就HuGM CSF的生物学功能及其在临床方面的应用做以下综述。     

Pulmonary defense and the human cathelicidin hCAP-18/LL-37

Antimicrobial peptides form an important component of the innate immune system. The cathelicidin family, a key member of the antimicrobial peptide defenses, has been highly conserved throughout evolution. Though widespread in mammals, there is currently only one identified human example, hCAP-18/LL-37. The cathelicidins have been found to have multiple functions, in addition to their known antimicrobial and lipopolysaccharide-neutralizing effects. As a result, they profoundly affect both innate and adaptive immunity. Currently, antimicrobial peptides are being evaluated as therapeutic drugs in disease states as diverse as oral mucositis, cystic fibrosis, and septic shock. One such peptide, the cathelicidin hCAP-18/LL-37, is reviewed in detail in the context of its role in lung physiology and defense.     

Canine cathelicidin (K9CATH): gene cloning, expression, and biochemical activity of a novel pro-myeloid antimicrobial peptide

Cathelicidins, a group of cationic peptides found in leukocytes and epithelial cells, play a central role in the early innate immune defense against infection. Although these host defense peptides have been reported in several mammalian species, including primates, no cathelicidins have been identified in carnivores. Here we report the cloning, tissue expression and biological activity of a novel canine cathelicidin (K9CATH). The full-length cDNA sequence of K9CATH encodes a predicted 172 amino acid pre-propeptide that is 60–70% similar to other mammalian cathelicidins. Mass spectrometry analysis confirmed that the 38 aa mature K9CATH peptide was present in neutrophil granule contents. Synthetic K9CATH displayed broad antimicrobial activity against Gram-positive bacteria (Listeria monocytogenes, and Staphylococcus aureus; MICs (minimal inhibitory concentrations) 0.5 and 50 μM, respectively), Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, Salmonella serotype Typhimurium, Pseudomonas aeruginosa, Proteus mirabilis; MICs 1.25 μM, Salmonella serotype Enteritidis; MIC 0.5 μM, and Neisseria gonorrhoeae; MIC 0.06 μM), and yeast (Candida albicans; MIC 12.5–50 μM). K9CATH demonstrated high antimicrobial activity against Ureaplasma canigenitalium, and lower activity against Ureaplasma urealyticum (MIC 0.06 and 50 μM, respectively). Similar to its ovine congener SMAP-29, K9CATH possesses salt-independent antimicrobial activity and LPS binding capacity. K9CATH displayed minimal hemolytic activity against human, dog and chicken erythrocytes. The potency and broad antimicrobial activity of K9CATH suggest that this peptide may act as a fundamental contributor to the innate immune responses in this carnivore species     

Augmentation of the bactericidal activities of human cathelicidin CAP18/LL-37-derived antimicrobial peptides by amino acid substitutions

Objective: Mammalian myeloid and epithelial cells express various peptide antibiotics (such as defensins and cathelicidins) that contribute to the innate host defense against invading micro-organisms. Among these, human cathelicidin CAP18/LL-37 (L¹-S³⁷) possesses potent antibacterial activities against Gram-positive and Gram-negative bacteria. In this study, to develop peptide derivatives with improved bactericidal actions, we utilized the amphipathic 18-mer peptide (K¹⁵–V³²) of LL-37 as a template, and evaluated the activities of modified peptides.Methods: Antibacterial activities of the peptides (0.022 ~ 4.4 M corresponding to 0.1 ~ 10 g/ml) were assessed by alamarBlue^TM assay using Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Escherichia coli and Pseudomonas aeruginosa as target organisms. Furthermore, the membrane-permeabilization activities of the peptides were examined by using E. coli ML-35p as a target.Results: By substituting E¹⁶ and K²⁵ with two L residues, the hydrophobicity of the peptide (18-mer LL) was increased, and by further substituting Q²², D²⁶ and N³⁰ with three K residues, the cationicity of the peptide (18-mer LLKKK) was enhanced. Among peptide derivatives, 18-mer LLKKK exhibited the most potent antibacterial actions against S. aureus (methicillin-resistant and -sensitive), S. pneumoniae, S. pyogenes, E. coli and P. aeruginosa, and possessed the most powerful membrane-permeabilizing activities against E. coli ML-35p at the effective concentrations (p < 0.05, 18-mer LLKKK vs. 18-mer LL, 18-mer K¹⁵-V³² and LL-37).Conclusions: Bactericidal activities of the amphipathic human CAP18/LL-37-derived 18-mer peptide can be augmented by modifying its hydrophobicity and cationicity, and 18-mer LLKKK is the most potent among peptide derivatives with therapeutic potential for Gram-positive and Gram-negative bacterial infections.Received 1 September 2004; returned for revision 1 October 2004; accepted by M. Katori 23 October 2004     

Antibacterial cathelicidin peptide CAP11 inhibits the lipopolysaccharide (LPS)-induced suppression of neutrophil apoptosis by blocking the binding of LPS to target cells

Objective: The action of antibacterial cathelicidin CAP11 (cationic antibacterial polypeptide of 11 kDa) on the lipopolysaccharide (LPS)-induced suppression of neutrophil apoptosis was evaluated in vitro.Methods: Human neutrophils (10⁶ cells/ml) were incubated alone or with mononuclear cells (6 × 10⁵ cells/ml) in the presence of LPS (10 ng/ml) and CAP11 (0.1 ~ 10 g/ml), and neutrophil apoptosis was determined.Results: LPS suppressed neutrophil apoptosis, accompanied with the activation of NF-B, phosphorylation of extracellular signal-related protein kinase (ERK), expression of Bcl-XL (an anti-apoptotic protein) and inhibition of caspase 3 activity. Interestingly, CAP11 (>1 g/ml) reversed the actions of LPS to trigger these changes, and induced neutrophil apoptosis (p < 0.0001). Moreover, neutralizing antibodies against Mac-1 (CD11b/CD18) and Toll-like receptor (TLR) 4 completely blocked the LPS-induced suppression of neutrophil apoptosis (p < 0.0001), suggesting a major role of Mac-1 and TLR4 in the LPS-mediated neutrophil activation. In addition, LPS activated monocytes to produce proinflammatory cytokines (IL-1, TNF- and IL-8) and inhibited neutrophil apoptosis. Importantly, CAP11 (>1 g/ml) reduced the cytokine production, thereby inducing neutrophil apoptosis (p < 0.0001). Finally, CAP11 (>1 g/ml) strongly suppressed the LPS-binding to neutrophils and monocytes (p < 0.01).Conclusions: CAP11 is able to block the LPS-induced survival of neutrophils via the suppression of anti-apoptotic signaling in neutrophils and cytokine production from monocytes by inhibiting the binding of LPS to target cells.Received 21 April 2004; returned for revision 10 June 2004; accepted by M. Katori 14 June 2004     

Human cathelicidin LL-37-derived peptide IG-19 confers protection in a murine model of collagen-induced arthritis

Current therapies for autoimmune chronic inflammatory diseases e.g. rheumatoid arthritis (RA) include inhibitors of inflammatory cytokines. However, these therapies can result in increased risk of infections. There is a need to explore alternate strategies that can control inflammation without compromising the innate ability to resolve infections. In this study, we examined the effect of small peptides derived from endogenous cathelicidin peptides in a murine model of collagen-induced arthritis (CIA). Cathelicidins are immunomodulatory peptides known to control infections. We demonstrate that the administration of the peptide IG-19, which represents an internal segment of the human cathelicidin LL-37, decreased disease severity and significantly reduced the serum levels of antibodies against collagen type II in the CIA model. IG-19 peptide reduced cellular infiltration in joints, prevented cartilage degradation and suppressed pro-inflammatory cytokines in the CIA mice. We also showed that not all cathelicidin-derived peptides exhibit similar functions. A bovine cathelicidin-derived peptide IDR-1018 did not exhibit the beneficial effects observed with the human cathelicidin LL-37-derived peptide IG-19, in the same murine model of CIA. This is the first study to provide evidence demonstrating the ability of a peptide derived from the human cathelicidin LL-37 to alleviate the arthritic disease process in a murine model of RA. Our results has lead us to propose a new approach for controlling autoimmune chronic inflammatory disorders such as RA, by using specific synthetic derivatives of endogenous host defence peptides. Cathelicidin-derived peptides are particularly attractive for their dual antimicrobial and anti-inflammatory actions.     

人抗菌肽hCAP18全长cDNA克隆及原核表达

目前发现，人体主要的抗菌肽有两大类；防御素（defensins）和cathelicidins。cathelicidins 家族成员中人类只有一个，即human cathelicidin antimicrobial peptide 简称hCAP18或LL-37。     

Expression of cathelicidin,ERK, MyD88, and TLR-9 in the blood of women in the pre-pregnancy,pregnancy, and their infant cord blood

During pregnancy, the immune responses are modulated to protect mothers and infants from different pathogens. Cathelicidin as an antimicrobial peptide has a defending role against many pathogens. In this study, to better understand the role of cathelicidin peptide and three of its related proteins in immune pathways (ERK, MyD88, and TLR-9) in the immune system during pregnancy, we examined their expression in the blood of non-pregnant and pregnant mothers and their infant’s cord blood. Blood samples were taken, and their peripheral blood mononuclear cells (PBMCs) were obtained. The expression level of cathelicidin was determined by quantitative PCR. Also, the expression of cathelicidin, ERK, MyD88, and TLR-9 was assessed by Western blotting. Higher level of cathelicidin mRNA was detected in the cord blood samples compared to other samples. The Western blotting results showed higher levels of cathelicidin, ERK, MyD88, and TLR-9 in the cord blood samples than in the blood of both pregnant and non-pregnant samples. Also, the level of all molecules was higher in pregnant than non-pregnant women. These high levels of the mentioned molecules are necessary to protect the mother and fetus against various pathogens, although understanding their mechanism of action needs more studies.