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Abstract

We investigated whether direct hemoperfusion with an immobilized polymyxin B column (DHP with PMX) could reduce the blood level of neutrophil elastase. 20 sepsis patients were enrolled in the study. DHP with PMX was performed twice within a 24-hour period. Neutrophil elastase was measured 7 times. Neutrophil elastase was 468 +/- 75.1 microg/l, while it was 1,531 +/- 201.7 microg/l immediately after the first session, declined to 351 +/- 73.9 microg/l before the second session of DHP with PMX, and increased again to 599.3 +/- 112.7 microg/l immediately after the second session, 328 +/- 73.7 microg/l at 24 h, 264 +/- 39.3 microg/l at 48 h, and 230 +/- 36.1 microg/l at 72 h after DHP with PMX. The levels from 48 h onwards were significantly lower compared with that before treatment. DHP with PMX has an overall effect that reduces circulating neutrophil elastase levels. (c) 2006 S. Karger AG, Basel

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Phagocytosing neutrophils produce and release high amounts of the neutrophil-activating peptide 1/interleukin 8

MA Cassatella, B Dewald, M Ceska … (1991)

After phagocytosis of yeast opsonized with IgG, neutrophil leukocytes (polymorphonuclear leukocytes [PMN]) expressed high levels of neutrophil-activating peptide 1/interleukin 8 (NAP-1/IL-8) mRNA, which peaked after 3-5 h and were still elevated after 18 h. A similar but quantitatively less prominent effect was obtained with lipopolysaccharide (LPS). After phagocytosis, but not after exposure to LPS, the PMN progressively released considerable amounts of NAP-1/IL-8 into the culture medium (18.6-50 ng/ml in 18 h). The peptide released was biologically active, as indicated by the transient elevation of cytosolic-free calcium in PMN exposed to aliquots of the culture supernatants, and desensitization by prestimulation of the cells with recombinant NAP-1/IL-8. By producing NAP-1/IL-8 at sites where they phagocytose invading microorganisms, PMN could enhance the recruitment of new defense cells.

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Circulating human peripheral blood granulocytes synthesize and secrete tumor necrosis factor alpha.

D. A. I. Spriggs, J Mannick, D Dubravec … (1990)

Circulating peripheral blood polymorphonuclear neutrophils (PMNs) have long been considered terminally differentiated cells that do not synthesize or secrete protein. However, work of others and ourselves has shown that PMNs can secrete the cytokine interleukin 1. In the present study we investigated whether circulating PMNs are capable of synthesizing and secreting another cytokine, tumor necrosis factor alpha (TNF-alpha). Highly purified (greater than 99% granulocytes) PMNs were isolated from normal human volunteer blood and cultured with or without bacterial lipopolysaccharide (LPS) for up to 24 hr. Cell culture supernatants were collected and tested for TNF-alpha, and total RNA was isolated from cells at various times after stimulation and assessed for TNF-alpha mRNA by Northern blot techniques. The results showed that message for TNF-alpha was produced after 60 min of in vitro stimulation with LPS and was maximal at about 4 hr. TNF-alpha was secreted into the supernatant of unstimulated PMNs from two different donors during 24 hr of culture (35-50 pg/ml), but significantly more (160-190 pg/ml) was secreted by PMNs when stimulated with LPS. PMNs from six other normal volunteers showed significant LPS-stimulated secretion of TNF at 60-180 min of culture. The secreted product also had biological activity against the TNF-sensitive L-M cell line, confirming that PMNs can make and secrete immunologically and biologically active TNF. Since it is also possible for monocytes to synthesize and secrete TNF, the amount of TNF secreted by a monocyte population equal to 20% of the PMNs cultured was measured. The results showed that monocytes at a concentration 20 times that potentially contaminating the PMN populations cultured could not produce as much TNF (unstimulated, 26-65 pg/ml; stimulated, 32-87 pg/ml). The PMN must now be considered a cell capable of altering the acute inflammatory response and modulating the immune response through the synthesis and release of cytokines.

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Elastase in tissue injury.

A Janoff (1984)

This article surveys elastinolytic proteinases in man, excluding enzymes of the pancreas and digestive tract. Special emphasis is placed on the elastase of polymorphonuclear neutrophils (PMN). The properties of this latter enzyme, its target molecules in plasma and connective tissues, and its endogenous regulators are briefly discussed. Persistent activity of the enzyme, even in the presence of its regulatory inhibitors, is explained. The chapter closes with a brief discussion of several pulmonary diseases in which elastase-mediated tissue injury is thought to play a role.

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PubMed ID:: 16391471

DOI:: 10.1159/000090593

ScienceOpen disciplines: Chemistry

Keywords: Adsorption,Adult,Aged,Aged, 80 and over,Female,Hemoperfusion,methods,Humans,Leukocyte Elastase,blood,chemistry,Male,Membranes, Artificial,Middle Aged,Polymyxin B,Sensitivity and Specificity,Time Factors

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Hemoperfusion with an immobilized polymyxin B column reduces the blood level of neutrophil elastase.

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Abstract

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Karger: Nephrology

Most cited references 13

Phagocytosing neutrophils produce and release high amounts of the neutrophil-activating peptide 1/interleukin 8

Circulating human peripheral blood granulocytes synthesize and secrete tumor necrosis factor alpha.

Elastase in tissue injury.

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