Search PubMed⌕ Search

Biomedical subjects

R M Senior

Publications and source records attributed to R M Senior.

At least 109 records · Page 6Linked to original sources
PubMed1981

Platelet factor 4 is chemotactic for neutrophils and monocytes.

Platelet factor 4 is shown to be a chemotactic protein for human polymorphonuclear leukocytes and monocytes at concentrations found in human serum and reached locally in injured tissue. The maximum chemotactic response to platelet factor 4 nearly equals that achieved with saturating concentrations of the chemotactic activity derived from the fifth component of human complement, C5. Cells desensitized to C5 chemotactic activity retain chemotactic responsiveness to platelet factor 4. Serum contains inhibitory capacity against the chemotactic activity associated with platelet factor 4. Our results suggest that the local release of platelet factor 4 may be an important stimulus attracting inflammatory cells to sites of blood vessel injury.

Blood Coagulation Factors↗
PubMed1981

Cell injury and repair.

Occupational lung disease results from a remarkably complex interaction of the inhaled material with the lung parenchyma and the worker's immune and inflammatory mechanism, (Fig 1). The past decade has seen a marked increase in our understanding of individual events involved in the pathogenesis of occupational lung disease, and has seen increased appreciation of the prominent role of lung inflammation in the production of lung disease following inhalation of a potentially injurious agent. Further work with isolated cells and tissue in culture and with experimental animal models will be required to assess the contribution of individual pathogenetic events to the total disease picture, and to better understand the ability of the lung parenchyma to repair itself following injury.

Chemotactic Factors↗
PubMed1980

111Indium-labeled human alveolar macrophages and monocytes: function and ultrastructure.

Human alveolar macrophages and peripheral blood mononuclear cells were labelled with indium-111 (111In)-oxine in ethanol. The efficiency of labeling averaged 84% for macrophages and 74% for mononuclear cell preparations. Phagocytosis by macrophages, the release of colony stimulating factor activity (CSF) by macrophages, and chemotaxis by monocytes in response to human C5-derived chemotactic factor (C5fr) and formyl-methionyl-leucyl-phenylalanine (f-MLP), were indistinguishable between labeled and unlabeled cells. Microscopically, labeled cells looked similar to control cells. Radioautography demonstrated 111In throughout the labeled cells, but there was a disproportionately high quantity over nuclei. These findings add to the growing literature indicating that 111In labels cells efficiently and that cells can retain function after being labeled with 111In.

Autoradiography↗
PubMed1980

Chemotactic activity of elastin-derived peptides.

Elastin-derived peptides, produced by digesting human aortic elastin and bovine ligament elastin with human neutrophil elastase, were tested for chemotactic activity. At 100 micrograms protein/ml, elastin digests were nearly as active for monocytes as saturating amounts of complement-derived chemotactic activity. Neutrophils and alveolar macrophages showed less response to elastin peptidces than did monocytes. Fractionation of the digests by gel filtration chromatography disclosed that maximal chemotactic activity eluted in fractions corresponding to 14,000-20,000 mol wt containing most of the desmosine cross-links in the digests. Whole human serum and rabbit anti-elastin immunoglobulin inhibited the chemotactic activity. Purified desmosine also showed chemotactic activity for monocytes, maximal at 10 nM. These findings suggest that elastin-degradation products enriched in cross-linking regions recruit inflammatory cells in vivo and that elastin proteolysis, characteristic of emphysema, may be a signal for recruitment of mononuclear phagocytes into the lungs.

Animals↗
PubMed1980

Phrenic nerve injury associated with venipuncture of the internal jugular vein.

Coincident with repeated, unsuccessful efforts to place a transvenous pacemaker through the right internal jugular vein, and 81-year-old man developed paralysis of the right hemidiaphragm. The patient had sudden shortness of breath and hypoxemia that rapidly subsided, although the loss of diaphragmatic function appears to be permanent.

Aged↗
PubMed1979

Receptor-mediated binding and internalization of leukocyte elastase by alveolar macrophages in vitro.

Radioiodinated leukocyte elastase was found to bind rapidly and specifically to alveolar macrophages in vitro. In contrast to the binding of pancreatic and bacterial proteases, leukocyte elastase binding did not require the presence of alpha 2 macroglobulin. The binding was inhibited by an excess of unlabeled enzyme and was saturable by increasing elastase concentrations. Leukocyte elastase binding thus met criteria for receptor-mediated binding, with and estimated association constant of 4.97 x 10(5) M-1 and an estimated total of 640 x 10(6) binding sites/cell. It differed from the previously described binding of lysosomal glycosidases to macrophages in that it was insensitive to trypsin pretreatment, did not require calcium ions, and was not inhibited by yeast mannan. High-resolution autoradiography indicated that the cell-associated radiolabeled leukocyte elastase was rapidly incorporated into phagolysosomes. Macrophage binding may have a role in clearance of leukocyte elastase from tissue sites where alpha 2 macroglobulin is absent or present in low concentration. Thus, enzyme uptake by alveolar macrophages may be an important factor in the amelioration of lung tissue injury by extracellular leukocyte elastase.

Autoradiography↗
PubMed1979

Digestion of the fifth component of complement by leukocyte enzymes. Sequential generation of chemotactic activities for leukocytes and for tumor cells.

Leukocytes contain within their lysosomal granules enzymatic activity that will generate from C5 chemotactic activity for leukocytes (neutrophils) and tumor (Walker carcinosarcoma) cells. Similar activity has been found in phagocytic supernatant fluids from neutrophils and in purified preparations of the leukocyte neutral proteases elastase and cathepsin G. White leukotactic activities can be generated from either the third (C3) or the fifth (C5) components of complement, only C5 serves as a source for generation of the chemotactic activity for tumor cells. As has been previously shown with trypsin, the C5-related chemotactic activities generated by leukocyte proteases are time-dependent: leukotactic activity appears early, then disappears, and is replaced by chemotactic activity for tumor cells. The generation of these chemotactic activities from C5 is blocked by prior treatment of leukocyte preparations with the neutral protease inhibitor Trasylol. The demonstration that enzyme activities from leukocytes have the ability to generate tumor cell chemotactic factors from C5 suggests a possible mechanism by which the development of metastatic lesions may be promoted at sites of tissue injury or inflammation.

Animals↗
PubMed1979

Biochemical quantitation of the chemotactic factor inactivator activity in human serum.

CFI of whole human serum was measured by a new assay that utilizes chemotactic factor-induced release of a lysosomal enzyme (N-acetyl glucosaminidase) from cytochalasin B-exposed neutrophils as an index of chemotactic activity. The effectiveness of serum as an inactivator of chemotactic factor-induced enzyme release closely correlated with the serum CFI as determined by assay of neutrophil chemotaxis in Boyden chambers. In comparison to serum from healthy persons, there was elevated CFI in the serum from patients with sarcoidosis and Hodgkin's disease by both assay systems. The results indicate that measurement of serum inhibition of chemotactic factor-induced lysosomal enzyme release from neutrophils provides a rapid, reliable, and reproducible assay of serum CFI. (J Lab Clin Med 93:17, 1979.)

Chemotaxis, Leukocyte↗
PubMed1977

Comparison of the elastolytic effects of human leukocyte elastase and porcine pancreatic elastase.

Porcine and bovine elastins were digested by human leukocyte elastase and porcine pancreatic elastase. The enzymes showed similarities in the extent to which they digested elastin and the pattern and quantitative distribution of N-terminal amino acids in the digests. However, fingerprints of the digests showed differences between the products of leukocyte elastase and pancreatic elastase. Each enzyme produced its characteristic fingerprint irrespective of whether the elastin substrate was obtained from ligament, pleura or lung parenchyma. The enzymes also digested tropoelastin differently. The results suggest that leukocyte elastase and pancreatic elastase should not be considered interchangeable in experimental models of tissue injury.

Amino Acid Sequence↗
PubMed1977

The induction of pulmonary emphysema with human leukocyte elastase.

Purified human leukocyte elastase was injected into the tracheas of 46 hamsters. Thirteen animals died spontaneously within 1 week, with extensive lung hemorrhage. The elastin content of the lungs was only slightly less than control values 3 hours after injection. At 2 months, the lungs of the remaining animals showed mild, patchy emphysema and morphometric changes consistent with emphysema. These results contrasted with the effects of a similar elastolytic dose of pancreatic elastase administered to 26 other hamsters in that only one animal died spontaneously, the lung elastin content 3 hours after injection was substantially decreased, and severe emphysema was present 2 months later. Leukocyte elastase appears to be capable of causing emphysema; but unlike pancreatic elastase, leukocyte elastase produces emphysema that is mild, even at a dose sufficient to produce intense lung hemorrhage and a high mortality.

Animals↗
PubMed1977

Chemotactic factor inactivators of human granulocytes.

During phagocytosis, neutrophils release a variety of substances that include activators and inactivators of chemotactic factors. It is generally considered that these represent hydrolytic enzymes. Elastase and cathepsin G, major proteases released from lysosomal granules during phagocytosis, contain broad hydrolytic activity. This study examined granule elastase and cathepsin G for their role as inactivators of chemotactic factors. Elastase and cathepsin G were purified from human neutrophils by Trasylol-Sepharose and CM-cellulose chromatography. Small amounts (approximately equal to 3 microgram, 1 muM) of elastase and cathepsin G, comparable to quantities released by 10(6) neutrophils during phagocytosis, completely inactivated the C5 chemotactic factor generated in human serum. Larger concentrations were needed to inactivate the C3 chemotactic factor, and when the bacterial chemotactic factor from Escherichia coli was employed, five times more elastase or cathepsin G was ineffective against this chemotactic factor. Supernatant fluid from human neutrophils that had ingested complement-coated zymosan particles contained elastase and cathepsin G and had inactivator activity for both the C5 chemotactic fragment and the bacterial factor. A specific inhibitor of elastase largely abolished the inactivator activity in the phagocytic supernates that was directed against C5 factor but did not affect the inactivator activity for the bacterial factor. Similar results occurred in studies of granule lysates. These data indicate heterogeneity in the chemotactic factor inactivator activity released by phagocytosing neutrophils. The predominant inactivator activity of the C5 chemotactic fragment is attributable to elastase and cathepsin G.

Cathepsins↗