Human peripheral blood polymorphonuclear leukocytes, when exposed to appropriate stimuli, generate significant amounts of superoxide anion (O-.2), a highly reactive molecule which is possibly involved in bacterial killing. Since the subcellular localization and mechanism activation O-.2 generating systems are unknown, we have investigated dismutase-inhibitable cytochrome c reduction (attributable O-.2) by, lysosomal enzyme release from, normal leukocytes cells rendered incapable ingesting...

Human PMN release lysosomal enzymes (ß-glucuronidase, acid phosphatase) when exposed to immune complexes, but do not cytoplasmic LDH. The cells remain viable, and failure of LDH appear in supernatants is due selective absorption or inactivation. Release platelet contamination only partially enhanced by fresh serum. after uptake complexes resembles that induced inert particles zymosan, can be distinguished from the concurrent all cell death membrane-lytic crystals MSU. Uptake MSU accompanied...

A low-molecular-weight component of complement, similar to or identical with human C5a, interacts polymorphonuclear leukocytes treated cytochalasin B and provokes extracellular release lysosomal enzymes from these cells. Enzyme occurs in the absence particles is selective that it not accompained by cytoplasmic enzymes. Cell viability altered. Pharmacologic agents regulate secretion other inflammatory mediators influenced complement-dependent enzyme release: cAMP theophylline, prostaglandin E...

To reduce the frequency of infection in acute leukemia, we employed isolation and air-filtration facilities ("protected environment") a prophylactic regimen that included oral nonabsorbable antibiotics. Eighty-eight randomized patients received identical remission-induction chemotherapy within one three groups: protected environment combined with (Group 1); antibiotics alone 2); neither nor prophylaxis 3). The groups were comparable factors might influence course leukemia susceptibility to...

Superoxide anion (O-2-) generation by human peripheral blood polymorphonuclear leukocytes is enhanced when these cells encounter appropriate soluble or particulate stimuli. O-2- requires intact, viable and proceeds independently of phagocytosis. To investigate the possibility that O-2--generating system associated with outer surface leukocyte plasma membrane, we have examined effects upon production p-diazobenzenesulfonic acid, a reagent which can react predominantly proteins external cell...

Human peripheral blood polymorphonuclear leukocytes were stimulated to generate thromboxane B2 in a time- and concentration-dependent fashion upon exposure serum-treated zymosan particles. Conversion by PMN of [14C] arachidonic acid [14C]thromboxane was confirmed thin-layer radiochromatography, radio-gas chromatography, mass spectrometry. Generation independent platelet contamination could be inhibited the cyclooxygenase inhibitor, indomethacin. Cells rendered incapable ingesting particles...

Leukotriene B4 (LTB,), formed by the 5-lipoxygenase pathway in human polymorphonuclear leukocytes (PMN), may be an important mediator of inflammation.Recent studies suggest that can convert LTB4 to products are less biologically active.To examine catabolism LTB,, we developed (using high performance liquid chromatography) a sensitive, reproducible assay for this and its w-oxidation (20-OH-and 20-COOH-LTB,).With assay, have found PMN (but not monocytes, lymphocytes, or platelets) exogenous...

Abstract Leukocyte lysosomes contain materials which interact with the complement system in at least two ways to generate C5-derived lysosomal enzyme-releasing activity (C5a). Firstly, a protease is capable of cleaving purified C5 neutral pH yield low molecular weight product selectively releases lysosomal, but not cytoplasmic, enzymes from isologous, cytochalasin B-treated, human polymorphonuclear leukocytes. The this enzyme inhibited by EACA and normal serum. Secondly, fresh serum, lysates...

We examined responses of human peripheral blood polymorphonuclear leukocytes (PMN) and monocytes to the highly purified complement-derived peptides C5a des Arg. As reported previously, proved be approximately 10- 20-fold more potent than Arg as a chemoattractant for PMN. also was in causing PMN acquire polarized morphology. In contrast, we found that do not distinguish between when these are used chemoattractants. two different assay systems, both acted at identical concentrations stimulate...

Abstract The alternate pathway of complement activation has recently assumed an important role in the mediation inflammation and tissue injury. We have found that activated via this interacts with human polymorphonuclear leukocytes (PMN) absence particulates stimulates selective release lysosomal enzymes. Fresh serum, after treatment zymosan or cobra venom factor, yields a fluid phase component which induces cytochalasin B-treated PMN to β-glucuronidase without leakage cytoplasmic lactate...

Two polymorphic forms of Fc receptor III (FcR III) are expressed on human neutrophils. These differ with respect to their apparent molecular masses after digestion N-glycanase, and reactivity MAb Gran 11 alloantisera which recognize determinants (NA1 NA2) the biallelic neutrophil antigen (NA) system. To determine basis for this polymorphism we isolated RNA from neutrophils NA1NA1 NA2NA2 homozygotes synthesized corresponding cDNAs. cDNAs encoding FcR were then amplified using polymerase chain...

To determine if biologically active products of complement appear during sepsis and to establish the relationship these components respiratory hemodynamic complications sepsis, we measured C5a des Arg C3a (radioimmunoassay), neutrophil chemotaxis, neutrophil-aggregating activity in plasma obtained from 40 patients at time was suspected clinically. Levels were elevated 35 38 patients, respectively, all 25 with positive blood cultures. Highest levels occurred hypotension (less than 90 mmHg)...

The optimal management of malignant intramedullary spinal cord astrocytomas remains controversial. Although radiotherapy has become the standard care, relationship between extent resection and survival unclear. We report outcomes surgical 35 assess association with after aggressive these tumors.An institutional tumor database (1990-2002) was reviewed to identify all patients treated for (anaplastic astrocytoma [AA] or glioblastoma multiforme [GBM]). Length from surgery charted by...

The dose-related inhibition by colchicine of both lysosomal enzyme release and microtubule assembly was studied in human polymorphonuclear leukocytes (PMN) exposed to the nonphagocytic stimulus, zymosan-treated serum (ZTS). Cells were pretreated with (60 min, 37 degrees C) or without cytochalasin B (5 microng/ml, 10 min) then stimulated ZTS (10%). Microtubule numbers B-treated untreated PMN increased stimulation depressed below resting levels a dose-response fashion concentrations above...

Cationic local anesthetics have been reported to influence cellular responses surface stimuli by interfering with the function of microtubules and microfilaments. Since unimpaired microtubule microfilament functions are required human polymorphonuclear leukocytes in order respond normally stimulation, we studied effects anesthetic, tetracaine on morphology these cells vitro. Tetracaine (0.25--1.0 mM) significantly reduced extracellular release lysosomal enzymes, beta-glucuronidase lysozyme...

Prostaglandin I2 (PGI2), a potent vasodilator and inhibitor of platelet aggregation, is major product arachidonic acid metabolism in endothelial cells that are derived from large blood vessels (e.g., umbilical veins). We have examined whether PGI2 also cultured dermal microvessels human newborn foreskin. Supernatants confluent monolayers had been incubated for 20 min with [3H]arachidonic the calcium ionophore A23187 (10 microM) were assayed prostaglandin F2 alpha (PGF2 alpha), E2 (PGE2),...

Human polymorphonuclear leukocytes (PMN) not only synthesize and respond to leukotriene B4 (LTB4), but also catabolize this mediator of inflammation rapidly specifically by omega-oxidation. To characterize the enzyme(s) responsible for omega-oxidation LTB4, human PMN were disrupted sonication subjected differential centrifugation yield membrane, granule, cytosol fractions (identified biochemical markers). LTB4 omega-hydroxylase activity was concentrated (together with NADPH cytochrome c...

Human neutrophils stimulated by concanavalin A (Con A, 100 microng/ml) contained markedly enhanced numbers of microtubules and discharged peroxidase-negative (specific) but not peroxidase-position (azurophile) granules. Release lysozyme from specific granules was dose time dependent, could be inhibitied alpha-methyl-D-mannoside, cytochalasin B. Many were associated with internalized plasma membrane bearing Con binding sites.

PMA enhanced release of the azurophil granule enzyme, beta-glucuronidase, as well lysozyme, from cytochalasin B-treated PMN's exposed to either zymosan particles or C5a. was active at nanomolar concentrations, not toxic cells, and most effective when present for brief durations (0-1 min) before exposure cells stimuli. Beta-glucuronidase released in significant amounts alone, absence stimuli such In contrast, only specific unstimulated cells. Electron micrographs revealed an increase number...