Cytolytic effects of neutrophils: role for a membrane-bound neutral proteinase

Journal Article · Sat Mar 01 04:00:00 EST 1986 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.83.6.1685· OSTI ID:5764534

Pontremoli, S; Melloni, E; Michetti, M; Sacco, O; Sparatore, B; Salamino, F; Damiani, G; Horecker, B L

A neutral serine proteinase, purified 250-fold from the plasma membrane fraction of human neutrophils, differs in its catalytic and molecular properties from the well-known neutral proteinases present in azurophil (primary) granules. Stimulation of neutrophils with low concentrations of phorbol 12-myristate 13-acetate (PMA) results in the release into the medium of the membrane-bound proteinase and the concomitant production of oxygen radicals. These concentrations of PMA also induce full cytolytic activity measured with /sup 51/Cr-labeled ox erythrocytes. A role for the neutral serine proteinase in the cytolytic activity of PMA-stimulated neutrophils is supported by the following observations: (i) the lytic activity of the stimulated neutrophils is correlated with the quantity of neutral proteinase present in the membranes; (ii) the extracellular medium from PMA-stimulated neutrophils causes the cytolysis of /sup 51/Cr-labeled erythrocytes that have been exposed to nonlytic concentrations of H/sub 2/O/sub 2/; (iii) cytolysis of H/sub 2/O/sub 2/-treated erythrocytes is also observed with the crude proteinase solubilized from neutrophil membranes or with the purified proteinase from the same source; and (iv) in each case the cytolytic activity is proportional to the proteinase activity present and is prevented by the addition of serine proteinase inhibitors. The authors conclude that cytolysis of target cells by PMA-activated neutrophils can result from the cooperative effects of oxygen radicals and the membrane-bound neutral serine proteinase.

• Research Organization: Univ. of Genoa, Italy
• OSTI ID: 5764534
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 83:6; ISSN PNASA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
BETA DECAY RADIOISOTOPES
BIOCHEMISTRY
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARCINOGENS
CELL CONSTITUENTS
CELL MEMBRANES
CHEMICAL REACTIONS
CHEMISTRY
CHROMIUM 51
CHROMIUM ISOTOPES
COBALT 57
COBALT ISOTOPES
DAYS LIVING RADIOISOTOPES
DECOMPOSITION
ELECTRON CAPTURE RADIOISOTOPES
ELEMENTS
ENZYMATIC HYDROLYSIS
ENZYMES
ERYTHROCYTES
ESTERS
EVEN-ODD NUCLEI
HYDROLASES
HYDROLYSIS
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
LEUKOCYTES
LYSIS
MATERIALS
MEMBRANES
NEUTROPHILS
NONMETALS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
OXYGEN
PEPTIDE HYDROLASES
PHORBOL ESTERS
RADIOISOTOPES
SOLVOLYSIS
TRACER TECHNIQUES