Inhibition by elastase inhibitors of the formyl met leu phe‐induced chemotaxis of rat polymorphonuclear leukocytes

Hornebeck, William; Soleilhac, Jean-Marc; Tixier, J. M.; Móczár, E.; Robert, L.

doi:10.1002/cbf.290050206

Cited by 35 publications

(16 citation statements)

References 23 publications

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“…Polarization is generally considered as a consequence of reorganization of microfilaments or disassembly of microtubles, both cytoskeletons which are effectors of locomotic and contractile responses of PMNS (Kelley et al 1984). Events subsequent to the bindig of fMLP to its receptor remain to be determined, although cell surface chymotrypsin-like proteinase, which can be inactivated by the inhibitors employed in the present study, has been implicated in transducing an intracellular cue for microfilament reorganization (Hornbeck et al 1987). On the other hand, the finding that the addition of proteinase inhibitors had no effect on colchicineinduced polarization supports direct disassembly of microtubles by colchicine without activation of the cell surface enzyme as previously indicated (Kelley et al 1984).…”

Section: Discussionmentioning

confidence: 89%

Effects of Proteinase Inhibitors on Polymorphonuclear Neutrophil Polarization.

Aoshiba¹,

Nagai

Takizawa

1991

Tohoku J. Exp. Med.

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Polarization of polymorphonuclear neutrophils (PMNs) can be elicited by the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) and the microtuble-disrupting compound colchicine. Here we report on whether natural and synthetic proteinase inhibitors alter the polarizing response to these two agents. The crl-proteinase inhibitor, N-tosyl-L-phenylalanine chloromethyl ketone, and N"-tosyl-L-lysine chloromethyl ketone suppress fMLP-induced polarization and locomotion in a dose-dependent fashion, but none of them affects colchicine-induced polarization. We suggest that proteinase inhibitors suppress fMLP-induced polarization by blocking cell surface proteinases that generate an intracellular signal for cytoskeletal change and polarization.

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Section: Discussionmentioning

confidence: 89%

Effects of Proteinase Inhibitors on Polymorphonuclear Neutrophil Polarization.

Aoshiba¹,

Nagai

Takizawa

1991

Tohoku J. Exp. Med.

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“…They showed that the inhibition of this enzyme by organophosphorus compounds reduced neutrophil chemotaxis (8,9) but were unsure as to the identity of the natural substrate or inhibitor (10). Other workers have reported that chloromethylketone inhibitors of chymotrypsin-like proteinases were able to suppress human neutrophil chemotaxis (11)(12)(13) and superoxide production (14) as well as attenuating membrane potential changes in rat neutrophils (15). Furthermore King and co-workers (16) reported that a monoclonal antibody against human neutrophils inhibited superoxide anion generation in response to the chemotactic peptide fMLP 1 by binding to a surface chymotrypsin-like enzyme.…”

mentioning

confidence: 99%

The Control of Neutrophil Chemotaxis by Inhibitors of Cathepsin G and Chymotrypsin

Lomas

Stone

Llewellyn-Jones

et al. 1995

Journal of Biological Chemistry

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Neutrophil chemotaxis plays an important role in the inflammatory response and when excessive or persistent may augment tissue damage. The effects of inhibitors indicated the involvement of one or more serine proteinases in human neutrophil migration and shape change in response to a chemoattractant. Monospecific antibodies, chloromethylketone inhibitors, and reactive-site mutants of ␣ 1 -antitrypsin and ␣ 1 -antichymotrypsin were used to probe the specificity of the proteinases involved in chemotaxis. Antibodies specific for cathepsin G inhibited chemotaxis. Moreover, rapid inhibitors of cathepsin G and ␣-chymotrypsin suppressed neutrophil chemotaxis to the chemoattractants N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) and zymosan-activated serum in multiple blind well assays and to fMLP in migration assays under agarose. The concentrations of antichymotrypsin mutants that reduced chemotaxis by 50% would inactivate free cathepsin G with a half-life of 1.5-3 s, whereas the concentrations of chloromethylketones required to produce a similar inhibition of chemotaxis would inactivate cathepsin G with a half-life of 345 s. These data suggest different modes of action for these two classes of inhibitors. Indeed the chloromethylketone inhibitors of cathepsin G (Z-GlyLeu-Phe-CMK) and to a lesser extent of chymotrypsin (Cbz-Gly-Gly-Phe-CMK) mediated their effect by preventing a shape change in the purified neutrophils exposed to fMLP. Antichymotrypsin did not affect shape change in response to fMLP even at concentrations that were able to reduce neutrophil chemotaxis by 50%. These results support the involvement of cell surface proteinases in the control of cell migration and show that antichymotrypsin and chloromethylketones have differing modes of action. This opens the possibility for the rational design of anti-inflammatory agents targeted at neutrophil membrane enzymes.

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“…Laminin is involved in the interaction between epithelial cells and basement membrane components, such as collagen type IV (5,6). Elastin was originally considered to be an isotropic and inert constituent, but physicochemical studies have pointed to a more dynamic structure and to possible interactions with other connective tissue proteins (7,8). Elastin peptides were also shown to be able to interact with several other cell types (9, 10).…”

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confidence: 99%

Inducible adhesion of mesenchymal cells to elastic fibers: elastonectin.

Hornebeck¹,

Tixier²,

Robert³

1986

Proc. Natl. Acad. Sci. U.S.A.

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The addition of highly purified elastic fibers to confluent human skin fibroblast or porcine aorta smooth muscle cell cultures resulted in a time-dependent, strong adhesion of the fibrils to the cell surface. The kinetics of adhesion was studied by video/time-lapse cinematography. After a 0.5-1 hr lag period, adhesion progressed to a maximum amount in 3-6 hr in the described conditions. Adhesion is strongly accelerated by the prior addition of soluble elastin peptides (K-elastin) to the cultures. Cycloheximide inhibits this induced adhesion. Adherent elastic fibers can be detached by treatment with elastase and trypsin but not with collagenase. The radioactive proteins adhering to elastic fibers, after a 6-hr incubation of the induced cultures in presence of [35S]methionine, were extracted and analyzed by NaDodSO4/PAGE. The proteins strongly adhering to the elastic fibers had apparent molecular sizes of about 120, 67, 60, and 45 kDa. Only the 120-kDa protein band showed a significant increase of its associated radioactivity in the induced cultures as compared to the noninduced cultures. We propose that the 120-kDa protein is responsible for the induced adhesion of mesenchymal cells to elastic fibers and designate it "elastonectin."In the past years, specific adhesive proteins that mediate cell attachment to the extracellular matrix have been identified and characterized. Fibronectin ensures the adhesion of mesenchymal cells to interstitial collagens and to some proteoglycans (1-4). Laminin is involved in the interaction between epithelial cells and basement membrane components, such as collagen type IV (5, 6). Elastin was originally considered to be an isotropic and inert constituent, but physicochemical studies have pointed to a more dynamic structure and to possible interactions with other connective tissue proteins (7,8). Elastin peptides were also shown to be able to interact with several other cell types (9, 10). Mecham et al. (11) studied the acquisition of chemotactic responsiveness to elastin peptides and the expression of the elastin phenotype by fetal bovine ligamentum fibroblasts during cell differentiation and showed that they were closely related events. Therefore, the investigation of whether specific protein(s) could mediate the adhesion of mesenchymal cells to elastic fibers was undertaken.In the present report, we have investigated the interactions between purified bovine ligamentum nuchae elastic fibers and human skin fibroblasts or pig aorta smooth muscle cells in culture and show that elastic fibers adhere strongly to both cell types. Fibronectin has been shown not to be involved in this process. Biosynthetic experiments carried out with human skin fibroblasts cultured in presence or absence of elastic fibers enabled us to carry out preliminary identification of an inducible protein closely associated with the added elastic fibers. We have designated this adhesive protein "elastonectin."MATERIAL AND METHODS Fibroblasts and smooth muscle cells were obtained from human dermis and porci...

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Inhibition by elastase inhibitors of the formyl met leu phe‐induced chemotaxis of rat polymorphonuclear leukocytes

Cited by 35 publications

References 23 publications

Effects of Proteinase Inhibitors on Polymorphonuclear Neutrophil Polarization.

Effects of Proteinase Inhibitors on Polymorphonuclear Neutrophil Polarization.

The Control of Neutrophil Chemotaxis by Inhibitors of Cathepsin G and Chymotrypsin

Inducible adhesion of mesenchymal cells to elastic fibers: elastonectin.

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