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A Janoff

Publications and source records attributed to A Janoff.

118 records · Page 7Linked to original sources
PubMed1968

Mediators of inflammation in leukocyte lysosomes. IX. Elastinolytic activity in granules of human polymorphonuclear leukocytes.

The present study demonstrates that a granule fraction derived from human polymorphonuclear leukocytes possesses elastinolytic activity, and that the latter can be separated from the collagenase present in these cells. Properties of the human leukocyte elastase differ sufficiently from those of pancreatic elastases of different species as to suggest that the former enzyme is a distinct and separate entity. Thus, soybean trypsin inhibitor and salivary kallikrein inhibitor (Trasylol) fail to inhibit elastolysis by the pancreatic enzyme, but do inhibit the leukocyte elastinolytic agent. Elastolysis by human leukocyte granule extract does not show significant salt inhibition, whereas that catalyzed by pancreatic elastase is markedly reduced when ionic strength is increased to physiological levels. The leukocyte granule extract is at least 10 times more resistant to serum elastase inhibitor than is the purified pancreatic enzyme. Both enzymes show optimal elastolysis above pH 8.5, but the leukocyte factor still retains 50% of its maximal elastolytic activity at pH 6-7; whereas the activity of the pancreatic enzyme falls to 10% or less of its maximal value under the same conditions. The foregoing characteristics of the human leukocyte elastase suggest that it, rather than pancreatic (serum) elastase, may mediate pathological elastolysis during acute arteritis in man. In keeping with this suggestion, the present experiments also show that elastica staining of human arterial vessels is reduced by incubation of tissues with human leukocyte granule extracts in vitro.

Adult↗
PubMed1968

Vascular injury and lysis of basement membrane in vitro by neutral protease of human leukocytes.

Frozen and thawed granules of human, peripheral-blood leukocytes rapidly produce hemorrhage when injected into animal tissues. The effect is blocked by inhibitors of proteolysis. The granule extract can digest vascular basement membrane in vitro at neutral pH. In addition, basement membranes of blood vessels damaged in vivo by the leukocyte fraction are found to be attenuated when examined by electron microscopy. The proteases of human leukocyte granules differ in several important respects from known lysosomal cathepsins and trypsin-like esterases. Polymorphonuclear neutrophils are a major source of the neutral proteases present in circulating white cells, and release these enzymes during phagocytosis of immune complexes.

Animals↗
PubMed1966

Mediators of inflammation in leukocyte lysosomes. VI. Partial purification and characterization of a mast cell-rupturing component.

The mast cell-rupturing component present in the lysosomes of rabbit exudate PMN neutrophil leukocytes has been identified and some of its physical and chemical properties have been described. The active agent is a low molecular weight (1200 to 2400) polypeptide containing a relatively large proportion of the basic amino acid, arginine. It is thermostable and dialyzable, and does not cause contraction of the isolated guinea pig ileum. The mast cell-rupturing activity of the agent is destroyed by trypsin. A second permeability factor with a larger molecular weight is present in crude extracts of PMN granules. Although this substance does not lyse mast cells, it is capable of evoking delayed permeability responses in rabbit skin.

Animals↗
PubMed1965

Mediators of inflammation in leukocyte lysosomes. II. Mechanism of action of lysosomal cationic protein upon vascular permeability in the rat.

The vascular permeability-increasing action of rabbit PMNL lysosomes has been studied in skin and cremaster muscle of the rat. Both an extract of frozen-thawed granules and a cathepsin-free cationic protein fraction of the granules (which had previously been demonstrated to cause leukocyte adhesion and emigration in vivo) induce increased vascular permeability in skin and muscle which resembles that produced by histamine or histamine-liberators with respect to the timing of the response and the predominant type of microvessel affected. Extracts of frozen-thawed lysosomes and the inflammatory lysosomal cationic protein both cause disruption of rat mesenteric mast cells in vitro, whereas a granule-free cytoplasmic fraction of PMN leukocytes and a non-inflammatory cationic protein fraction of the granules do not do so under identical test conditions. The mastocytolytic action of lysosomal materials in vitro is not inhibited in the presence of 10 kallikrein-inhibiting units of trasylol per ml. The mast cell rupturing fraction of PMNL granules (cationic protein) possesses no detectable peroxidase activity or acid-mucopolysaccharase activity. When compared with compound 48/80 on the basis of estimated molecular weight, the lysosomal cationic protein appears to be at least as active as the latter compound with respect to in vitro mastocytolytic potency. Chronic pretreatment of rats with an agent known to reduce tissue mast cell numbers causes marked suppression of the vascular permeability change normally induced in skin and muscle by lysosomal extracts and cationic protein. Similar results are obtained if lysosomal materials are tested in rats pretreated with an antihistaminic. These observations are discussed with respect to the mode of action of PMNL lysosomes in the early and late phases of local tissue-injury reactions.

Animals↗
PubMedDate not supplied

Identification of neutral proteases in human neutrophil granules that degrade articular cartilage proteoglycan.

Human polymorphonuclear neutrophil (PMN) granule extract (25 mug of protein) released 60 percent of the available 35SO4 from labeled rabbit articular cartilage in 0.5 hour at neutral pH. N-acetyl-L-alanyl-L-alanyl-L-prolyl-L-alanine choloromethyl ketone (NAcAAPACK), a specific elastase inhibitor, was only minimally effective against whole granule extract, and N-alpha-tosyl-L-lysine chloromethyl ketone, which inhibits trypsin but not elastase, was completely ineffective. Preparative disc-gel electrophoresis of PMN granule extract revealed two separate regions with independent activity against 35SO4-labeled cartilage. One region contained elastases and when tested alone, was completely inhibited by NAcAAPACK. The other contained lysozyme and two esterases active against N-acetyl-L-phenylalanine-alpha-naphthol. Purified lysozyme proved inactive, suggesting that the chymotrypsin-like esterases were responsible for proteoglycan degradation by this region of the gel.

Animals↗
PubMedDate not supplied

Assessment of elastase-induced structural and functional changes in sheep lungs.

A large-animal model of elastase-induced emphysema is being developed, which permits the evaluation of corresponding changes in lung structure and function under controlled conditions. Varying doses of elastase were instilled intrabronchially into the lower right lobes of 12 sheep. Changes in regional distribution of lung perfusion (Q) and ventilation (V), corrected for lung volume, were determined from in vivo measurements with radioactive Tc-99m MAA, Kr-81m and Xe-127, respectively, before and four weeks after elastase treatment. Lung injury was assessed by histological examinations of tissue removed post mortem. A positive correlation (r = 0.74; p less than 0.01) was observed between the dose of instilled elastase (range: 800-8,000 units) and a reduction in Q. A decrease in Q also correlated significantly (r = 0.63; p less than 0.05) with an increase in alveolar mean linear intercept (Lm). V also decreased with increasing dose of elastase and with increasing Lm, but the results did not attain statistical significance. These results suggest that computer analysis of regional Q and V by radionuclide imaging techniques represents a reliable, sensitive and non-invasive means of assessing elastase-induced pulmonary injury in the sheep.

Animals↗