Alveolar Wall Apoptosis Causes Lung Destruction and Emphysematous Changes

Aoshiba, Kazutetsu; Yokohori, Naoko; Nagai, Atsushi

doi:10.1165/rcmb.2002-0090oc

Cited by 324 publications

(241 citation statements)

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“…The researchers have used Pep-1 for the delivery of protein kinase A (PKA) into distal lung epithelial cells of rat in order to correct the defect in protein kinase. Pep-1 strategy was also applied for evaluation of the anti-tumoral activity of peptide inhibitors of protein kinase or of antisense PNAs targeting cyclin B1, via intratumoral injections as well as for the delivery of antibodies and protein into immature bovine and mouse oocytes, which offers a potent tool for studying early embryonic development (21,(25)(26)(27). For most proteins and peptides, optimal complex formation was achieved for a Pep-1: cargo molar ratio of 20:1 as reported in our studies.…”

Section: Discussionmentioning

confidence: 99%

“…A major key for successful protein transfer into cells is the development of protein delivery systems with high efficiency and low cytotoxicity (19). Pep-1 as a cell penetrating peptide has been effectively used to transfer different cargoes (peptide nucleic acids or PNAs, peptides, and proteins) into the cells (20)(21)(22)(23)(24)(25)(26)Gros et al,personal communication). Several advantages of the noncovalent complexes of Pep-1/cargo contain: (a) rapid delivery of proteins into cells with high efficiency, (b) stability in physiological buffers, and (c) lack of toxicity and sensitivity to serum.…”

Section: Introductionmentioning

confidence: 99%

“…It involves transient membrane disorganization along with folding of Pep-1 into a helical structure within the phospholipids membrane (27,28). Many types of proteins, antibodies, and peptides were successfully delivered into different cell lines using Pep-1 strategy and were represented to retain their full biological activity (20)(21)(22)(23)(24)(25)(26)Gros et al,personal communication). In this study, the potency of Pep-1 cell penetrating peptide was assessed for HPV16 E7 protein delivery in vitro.…”

Section: Introductionmentioning

confidence: 99%

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Protein vaccination with HPV16 E7/Pep‐1 nanoparticles elicits a protective T‐helper cell‐mediated immune response

et al. 2016

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Two human papillomavirus (HPV) viral oncoproteins, E6 and E7 represent ideal targets for development of a therapeutic HPV vaccine. It is important to reduce the rate of HPVassociated malignancies through improvement of vaccine modalities. In this study, we used a short amphipathic peptide carrier, Pep-1, for delivery of the full-length HPV16 E7 protein into mammalian cells and evaluated immune responses and protective effects of different formulations in C57BL/6 tumor mice model. Our results showed that the complexes of E7/ Pep-1 protein form stable nanoparticles through noncovalent binding with an average size of 120 to 250 nm. The efficient delivery of E7 protein by Pep-1 at molar ratio of 1:20 was detected in HEK-293T cell line for 1 h and 3 h posttransfection. Immunization with E7/Pep-1 nanoparticles at a ratio of 1:20 induced a higher Th1 cellular immune response with the predominant IgG2a and IFN-c levels than those induced by E7 protein in a murine tumor model. These data suggest that Pep-1 peptide would indicate promising applications for improvement of HPV therapeutic vaccines. V C 2016 IUBMB Life, 68(6): [459][460][461][462][463][464][465][466][467] 2016

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Protein vaccination with HPV16 E7/Pep‐1 nanoparticles elicits a protective T‐helper cell‐mediated immune response

et al. 2016

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“…In the context that there is more cell turnover in smokers and individuals with COPD (25)(26)(27)(28)(29)(30)(31)(32)(33)(34), the observation that MERTK is up-regulated and functional in the AMs of smokers may reflect several important findings. It may reflect not only an increased demand for removal of apoptotic cells but also an effort to compensate for the lack of up-regulation or dysfunction of other apoptotic cell removal receptors which would ultimately decrease the inflammatory burden in the lungs of smokers.…”

mentioning

confidence: 99%

Overexpression of Apoptotic Cell Removal Receptor MERTK in Alveolar Macrophages of Cigarette Smokers

Kazeros

Harvey²,

Carolan³

et al. 2008

Am J Respir Cell Mol Biol

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Mononuclear phagocytes play an important role in the removal of apoptotic cells by expressing cell surface receptors that recognize and remove apoptotic cells. Based on the knowledge that cigarette smoking is associated with increased lung cell turnover, we hypothesized that alveolar macrophages (AMs) of normal cigarette smokers may exhibit enhanced expression of apoptotic cell removal receptor genes. AMs obtained by bronchoalveolar lavage of normal nonsmokers (n 5 11) and phenotypic normal smokers (n 5 13; 36 6 6 pack-years) were screened for mRNA expression of all known apoptotic cell removal receptors using Affymetrix HG-U133 Plus 2.0 microarray chips with TaqMan RT-PCR confirmation. Of the 14 known apoptotic receptors expressed, only MER tyrosine kinase (MERTK), a transmembrane tyrosine kinase receptor, was significantly up-regulated in smokers. MERTK expression was then assessed in AMs of smokers versus nonsmokers by TaqMan RT-PCR, immunocytochemistry, Western analysis, and flow analysis. Smoker AMs had up-regulation of MERTK mRNA levels (smoker vs. nonsmoker: 3.6-fold by microarray, P , 0.003; 9.5-fold by TaqMan RT-PCR, P , 0.02). Immunocytochemistry demonstrated a qualitative increase in MERTK protein expression on AMs of smokers. Increased protein expression of MERTK on AMs of smokers was confirmed by Western and flow analyses (P , 0.007 and P , 0.0002, respectively). MERTK, a cell surface receptor that recognizes apoptotic cells, is expressed on human AMs, and its expression is up-regulated in AMs of cigarette smokers. This up-regulation of MERTK may reflect an increased demand for removal of apoptotic cells in smokers, an observation with implications for the development of chronic obstructive pulmonary disease, a disorder associated with dysregulated apoptosis of lung parenchymal cells.Keywords: apoptosis; MER tyrosine kinase; alveolar macrophages MER receptor tyrosine kinase (MERTK), a 110-kD transmembrane protein member of the receptor tyrosine kinase family of cell surface receptors, plays a role in the clearance of apoptotic cells (1-4). The MERTK gene is normally expressed on mononuclear phagocytes, dendritic cells, retinal pigment epithelial (RPE) cells, and reproductive tissue (5-8). In mice, deletion of MERTK results in delayed clearance of apoptotic cells and development of autoimmune disease (1, 9, 10). In humans, mutations in MERTK result in retinitis pigmentosa, a disease characterized by a defect in the RPE phagocytosis pathway, where the RPE cells are unable to ingest the shed apoptotic tips of photoreceptor cells (11)(12)(13)(14).In the lung, the clearance of apoptotic cells is the normal function of alveolar macrophages (AMs), the monocyte-derived pulmonary representative of the mononuclear phagocyte system (15-18). Because phagocytosis of apoptotic cells by mononuclear phagocytes invokes an array of receptors on the phagocyte that interacts with bridging molecules and cell-specific ligands on the apoptotic cells, the control of expression of apoptotic receptors on the phagocyte plays ...

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“…[22][23][24][25] Induction of apoptosis by active caspase-3 instillation in mice caused architectural changes in the lungs similar to those observed in human emphysema. 26 Oxidant stress, such as that resulting from cigarette smoke, results in the killing of lung cells by both apoptosis and necrosis. Glutathione S-transferase was shown to have a protective effect on tobacco smoke-induced apoptosis.…”

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confidence: 99%

Angiotensin II in apoptotic lung injury: potential role in meconium aspiration syndrome

Uhal

Abdul-Hafez

2008

J Perinatol

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Meconium aspiration injures a number of cell types in the lung, most notably airway and alveolar epithelial lining cells. Recent data show that at least some of the cell death induced by meconium occurs by apoptosis, and therefore has the potential for pharmacologic inhibition through the use of apoptosis blockers or other strategies. Related work in adult animal models of lung injury has shown that apoptosis of lung epithelial cells induces a local (that is, entirely lung tissue specific) renin-angiotensin system (RAS L ). Furthermore, this inducible RAS L is required for the apoptotic response and affects other adjacent cell types through the release of angiotensin II and related peptides. This manuscript reviews the published data supporting this viewpoint as well as more recent works that suggest the involvement of a RAS L in the perinatal lung damage associated with meconium aspiration syndrome (MAS). The implications of these findings regarding their potential for the clinical management of MAS are also discussed.

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Alveolar Wall Apoptosis Causes Lung Destruction and Emphysematous Changes

Cited by 324 publications

References 23 publications

Protein vaccination with HPV16 E7/Pep‐1 nanoparticles elicits a protective T‐helper cell‐mediated immune response

Protein vaccination with HPV16 E7/Pep‐1 nanoparticles elicits a protective T‐helper cell‐mediated immune response

Overexpression of Apoptotic Cell Removal Receptor MERTK in Alveolar Macrophages of Cigarette Smokers

Angiotensin II in apoptotic lung injury: potential role in meconium aspiration syndrome

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