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PubMed1987

Complement-induced equine neutrophil adhesiveness and aggregation.

Equine neutrophils (PMN) were isolated from citrated normal blood by density gradient separation on Ficoll-Hypaque to greater than 96% purity and 98% viability and an average of 3.78 x 10(7) PMN/ml. The agonist C5a des Arg was used in serial dilutions of whole zymosan-activated equine plasma (ZAP) or was partially purified from ZAP by column chromatography. Purified equine PMN exhibited rapid aggregation following incubation with C5a des Arg which was further dependent on the availability of divalent cations, especially Mg++. The microfilament disruptive agent cytochalasin B (5 micrograms/50 microliters) greatly augmented aggregation responses to C5a des Arg. Subaggregating doses of C5a des Arg promoted PMN adhesiveness as assayed on 0.5 x 10 cm borosilicate glass columns containing a 2.0 cm bed of Sephadex G-25. This C5a des Arg-induced increased adhesiveness was inhibitable by prior incubation of the PMN with either non-steroidal (0.065 M phenylbutazone) or steroidal (0.005 M dexamethasone) anti-inflammatory agents. Ultrastructural studies correlated well with functional assays and revealed marked organelle-free lamellipodia formation without PMN-PMN contact at subaggregating doses of the agonist and progressive PMN-PMN contact at aggregating doses. Equine PMN are responsive to C5a des Arg, and induced adhesiveness responses can be manipulated by anti-inflammatory agents.

Animals↗
PubMed2006

New prognostic markers in CLL.

The individual prognosis of patients with chronic lymphocytic leukemia (CLL) is extremely variable. Although clinical stages remain the basis for assessing prognosis in CLL, a number of biological markers, particularly serum markers, cytogenetic abnormalities, IgVH mutations, CD38 and ZAP-70 expression in leukemic cells offer important, independent prognostic information. Before being incorporated into daily practice, however, these markers require standardization and validation in large, prospective trials. Meanwhile, treatment of patients with CLL not included in clinical studies should be decided on the basis of classical NCI/CLL Working Group criteria. An important area of research in CLL prognostication is the identification of markers useful for predicting response to therapy and its duration. Among them, del(17p), reflecting P53 abnormalities, is particularly important. Also relevant is del(11q), which points to ATM defects. There is also some correlation between IgVH mutational status, ZAP-70 and CD38 expression and response to therapy and its duration, although these relationships need further investigation. Finally, there is increasing evidence that response to therapy, particularly in those cases in which minimal residual disease is eradicated, is associated with longer survival.

Biomarkers↗
PubMed2005

Prognostic usage of V(H) gene mutation status and its surrogate markers and the role of antigen selection in chronic lymphocytic leukemia.

B-cell chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease with many patients surviving for decades with minimal or no treatment, whereas others succumb rapidly to their disease despite therapy. In recent years, new molecular prognostic factors have emerged in CLL that have significantly improved the subgrouping of the disease. One of the most important molecular predictors, the immunoglobulin V(H) gene mutation status, divides CLL into two prognostic groups, depending on the presence or absence of somatic hypermutation, where unmutated V(H) genes are associated with considerably worse prognosis than mutated V(H) genes. An exception to this appears to be CLL patients utilizing the V(H)3-21 gene as they have poor outcome irrespective of mutation status. Surrogate markers for the VH gene mutation status have been suggested, such as CD38 and ZAP-70 expression. However, the CD38 level was later shown to display poor correlation to the mutation status, although it may still serve as an independent prognostic factor. More promising is the expression levels of ZAP-70, which appears to be both a strong surrogate marker for V(H) gene mutation status, although discrepancies have been reported, as well as an independent prognostic marker. Immunoglobulin gene analysis has also indicated the possibility of antigen selection in CLL considering the significant bias in V(H) gene usage. Intriguingly, the V(H)3-21+ group and several other CLL subsets using certain V(H) genes was recently reported to display strikingly restricted immunoglobulin gene features, in both their heavy and light chain gene rearrangements, thus further high-lighting the possible role of antigen involvement in CLL development.

Antigens, Neoplasm↗
PubMed2000

Association among filamentous actin content, CD11b expression, and membrane deformability in stimulated and unstimulated bovine neutrophils.

OBJECTIVE: To investigate rheologic properties of bovine neutrophils that may result in adhesion molecule-independent sequestration of neutrophils in inflamed lungs of cattle. ANIMALS: Healthy 2- to 4-week-old male Holstein calves. PROCEDURES: Neutrophil deformability, filamentous actin (F-actin) content, and CD11b expression was determined for unstimulated bovine neutrophils and bovine neutrophils incubated with the inflammatory mediators tumor necrosis factor-alpha (TNF), platelet-activating factor (PAF), interleukin-8 (IL-8), zymosan-activated plasma (ZAP), Pasteurella haemolytica-derived lipopolysaccharide (LPS), and P haemolytica leukotoxin. Neutrophils were separated into 3 subpopulations on the basis of size. The Factin content and CD11 b expression were evaluated by use of flow cytometry. Leukocyte deformability was evaluated by filtration of dilute whole blood. RESULTS: The subpopulation of the smallest-sized neutrophils (>90% of neutrophils) contained little F-actin. A subpopulation of slightly larger neutrophils had a profound increase in F-actin content and CD11 b expression. The subpopulation of the largest neutrophils had increased F-actin content and CD11b expression, compared with those for both subpopulations of smaller neutrophils. Incubation of neutrophils with PAF and ZAP but not TNF, IL-8, LPS, or leukotoxin, resulted in decreased neutrophil deformability and increased F-actin content. Incubation with PAF and TNF induced an increase in size of neutrophils. CONCLUSIONS AND CLINICAL RELEVANCE: Size can be used to identify subpopulations of large and rigid neutrophils in blood samples from healthy calves. Platelet-activating factor and activated complement fragments are potent inducers of F-actin formation and neutrophil rigidity. Physical changes in neutrophils may impede their transit through lung microvasculature and result in leukocyte trapping independent of adhesion molecule interactions with endothelial cells.

Actins↗
PubMed1999

Pre-T cell receptor signals are responsible for the down-regulation of Syk protein tyrosine kinase expression.

Thymocyte development proceeds through two critical checkpoints that involve signaling events through two different receptors, the TCR and the pre-TCR. These receptors employ two families of protein tyrosine kinases to propagate their signals, the Src and Syk families. Genetic and biochemical evidence has shown that the Src family kinases are critical for normal T cell maturation. ZAP-70, a Syk family kinase, has similarly been implicated as a critical component in thymocyte development. Although genetic evidence has suggested that Syk is involved during thymocyte development, a definitive study of Syk expression has not been performed. In this paper we report our reanalysis of Syk expression in subpopulations of murine and human thymocytes by intracellular staining and flow cytometry using anti-Syk mAbs. Syk is expressed at increased levels during the stages in which pre-TCR signaling occurs. Furthermore, Syk is down-regulated after the pre-TCR checkpoint has been passed. Syk may play an important role in thymic development during pre-TCR signal transduction. Finally, incomplete down-regulation of Syk expression was noted in human thymocytes, offering a possible explanation for the distinct phenotypes of mice and humans deficient in ZAP-70.

Animals↗
PubMed2000

[Gene expression in white blood cells in chronic myeloid leukemia].

BACKGROUND: The new technologies that have the DNA laboratory over recent years and the general progress in knowledge of the human genome, have allowed the simultaneous observation of the activity of a large number of genes. Chronic myeloid leukemia is characterized with abnormal tyrosine kinase activity of the fused bcr/abl gene, which is most often product of translocation between chromosomes 9 an 22. It is as yet unknown whether this is the only and sufficient cause of the disease, or whether other supporting and co-active abnormalities exist. It is also not yet clear whether an increase of proliferating activity or reduced programmed cell death plays the dominant role. The aim of this study was to make further steps in resolving the question as to which of these hypotheses fits better. METHODS AND RESULTS: Membrane macroarrays (Clontech 7742-1: Human Cancer cDNA Expression Array with 588 gene probes) were used throughout the study, on which cDNA reverse-transcribed from total RNA in turn isolated from peripheral white blood cells and labelled with 32P was hybridized. Cells obtained from 5 patients with confirmed diagnoses by cytogenetic and molecular (bcr/abl) analyses, but who had not yet been treated by chemotherapy, were the source of the material. In some cases mononuclears and granulocytes were also isolated by Ficoll-Paque centrifugation. Radioactivity was detected by autoradiography or by a Phosphorimager (Fujifilm FLA-2000). Comparison with normal gene expression (healthy donor) was made by subtraction using Clontech AtlaImage 1.5 software. Although changes of expression of identical genes were not observed in all of patients examined, the majority of them were concordant. Values at least double those of the controls applied to the activity of c-jun N-terminal kinase, MMP-8, MMP-9, integrin alpha E, integrin beta and PDGF, whereas the expression of ZAP-70, IRF1, MCL-1, STAT 5B, RARA, CDC25B, RPSA, TNFR decreased. Increases of PCNA, MMP-17, CD59, rho G, CRAF1 and PIG7 or decreases of notch, caspase 8, caspase 4, interleukin 6 receptor, rho B and TIMP1 were observed only in some cell samples. CONCLUSIONS: It seems that some maturation processes and transmembrane signalling are blocked, as well as the effectors of apoptosis. On the other hand, the reduced activity of ZAP-70, IRF1 and MCL-1 also indicated that proliferation breaks were weakened. The involvement of both processes-released replication and ineffective apoptosis--was evident; the problem of bcr/abl gene fusion being the necessary first and sufficient step on the way towards developing chronic myeloid leukemia, however, remained unresolved.

Fusion Proteins, bcr-abl↗
PubMed2001

[Construction of cDNA library of Eimeria tenella sporulated oocysts].

A lambda ZAP express cDNA library was constructed using mRNA from Eimeria tenella sporulated oocysts. Total RNA was isolated by the TRIzol from Eimeria tenella sporulated oocysts, mRNA was further purified through oligo(dT)-cellulose columns. The first-strand cDNA was synthesized by using MMLV reverse transcriptase with oligo(dT)18 primers containing Xho I restriction site. After the second strand cDNA replacement synthesized, the uneven termini of the double-stranded cDNA were filled in with cloned Pfu DNA polymerase and EcoR I adapters were ligated to the blunt ends. Then the double-strand cDNA was digested with Xho I restriction enzyme. The fragments of 0.5 kb-4 kb were collected by agarose gel fraction method. After ligation of the cDNA with the lambda ZAP Express vector, the cDNA library was packaged using Gigapack III Gold Packaging extract. According to the phage plaques bright selection, the cDNA library contained 6 x 10(6) clones and the titer of the amplified library was 1 x 10(11) pfu/mL. By using PCR identification, the cDNA library contained approximately 96% recombinant phages.

Animals↗
PubMed2003

Identification and characterization of human TIPARP gene within the CCNL amplicon at human chromosome 3q25.31.

Array CGH combined with mRNA microarray analyses was successfully applied for genome-wide screening of proto-oncogenes as well as tumor suppressor genes in 2002. It has been reported that an uncharacterized gene, corresponding to a 5'-truncated partial cDNA DKFZp434J214, is amplified and up-regulated together with CCNL in head-and-neck squamous cell carcinoma (HNSCC). Here, we identified that the novel gene, corresponding to the 5'-truncated DKFZp434J214 cDNA, is the human ortholog of mouse Tiparp gene, by using bioinformatics. Complete coding sequence of human TIPARP mRNA was determined in silico by assembling nucleotide sequences of BC034397 and DKFZp434J214 cDNAs. Human TIPARP gene, consisting of six exons, was located between SSR3 and CCNL genes at human chromosome 3q25.31. Fugu tiparp gene was located around nucleotide position 14280-23355 of fugu genome draft sequence CAAB01003597.1. Human TIPARP showed 91.8% and 52.7% total amino-acid identity with mouse Tiparp and fugu tiparp, respectively. TPH domain (codon 242-296 of human TIPARP), WWE domain (codon 329-378) and PARP-like domain (codon 465-648) were evolutionarily conserved among TIPARP proteins. CCCH-type zinc finger was located within the N-terminal part of the TPH domain. Human TIPARP showed 27.5% and 26.0% total-amino-acid identity with human FLJ22693 and ZAP, respectively. TIPARP, FLJ22693 and ZAP, sharing the common structure with the TPH, WWE and PARP-like domains, were found to constitute the TIPARP family. This is the first report on human TIPARP and fugu tiparp genes as well as on the TIPARP family.

Amino Acid Sequence↗
PubMed1992

The influence of thymus extracts on the chemotaxis of polymorphonuclear neutrophils (PMN) from patients with insulin-dependent diabetes mellitus (IDD).

The main goal of this study was to evaluate the possible influence of thymus extracts on the chemotaxis of PMN isolated from diabetic patients. The analyzed group consisted of fifty patients with insulin-dependent diabetes mellitus (IDD), and twenty healthy adults were taken as controls. The results showed, that PMN isolated from patients with IDD manifested the impaired chemotaxis toward zymosan-activated plasma (ZAP), plasma incubated with cellophane and supernate from E. coli culture. Both thymus extracts did not change the directed migration toward control plasma and toward ZAP. THYMEX-L did improve the migration of diabetic PMN toward plasma incubated with cellophane, whereas TFX-THYMOMODULIN ameliorated the impaired chemotaxis toward supernate from E. coli culture. Both thymus extracts can attract PMN obtained from healthy donors, but not the cells isolated from diabetic patients.

Adolescent↗
PubMed1992

A tyrosine-phosphorylated 70-kDa protein binds a photoaffinity analogue of ATP and associates with both the zeta chain and CD3 components of the activated T cell antigen receptor.

An early event in T cell antigen receptor (TCR)-mediated signal transduction is the activation of a protein tyrosine kinase (PTK) pathway. An unidentified PTK activity and a kinase substrate termed ZAP-70 have previously been shown to associate with TCR zeta upon cross-linking of TCR beta. Here we report that TCR activation, by antibody cross-linking of either TCR beta or CD3 epsilon, results in the association of a PTK activity with both CD3 and TCR zeta. A number of in vitro PTK substrates are also associated with CD3 and TCR zeta, including CD3 epsilon, TCR zeta, p60fyn, p62yes, and a predominant 70-kDa protein (ZAP-70). The shared PTK activity and PTK substrates suggest that both CD3 and TCR zeta are involved in signal transduction via a shared pathway. We used [alpha-32P]gamma-azidoanilido ATP, a photoreactive analogue of ATP, to detect CD3-associated proteins that bound ATP upon TCR activation, reasoning that such proteins could represent PTKs. A 70-kDa protein bound [alpha-32P]gamma-azidoanilido ATP only upon TCR activation, and we propose that this protein and the 70-kDa PTK substrate are the same protein. Furthermore, we propose that this protein is responsible for the PTK activity observed to be associated with TCR zeta and CD3 upon TCR activation.

Adenosine Triphosphate↗
PubMed1990

[Pathoanatomical and pathophysiological study of lung injury induced by activated complement in rat].

Acute lung injury induced by intravenous infusion of zymosan-activated plasma(ZAP) on Wistar rats was studied. A single infusion of ZAP resulted in an early occurrence of increased respiratory rate, decreased PaO2, elevated activity of superoxide dismutase(SOD) in the arterial blood and lung tissue. The results showed that the content of copperzinic superoxide dismutase(Cu Zn SOD) in bronchiolar columnar epithelial cells was elevated. Histological and electron microscopic examination showed that there was an accumulation of neutrophils in pulmonary microvessels and capillaries, endothelial cell and epithelial cell injury, and pulmonary edema etc. The tight junctions both in the epithelium and endothelium showed alterations in substructure including discontinuity, irregularity, free ends and distention of meshes as early as 2 to 4 h. In later stage, the severity of damage of tight junctions increased, while the number of strands in endothelial junctions reduced. All the parameters in the control group did not change significantly. From the results, the authors consider that acute lung injury is intimately related to the neutrophils and oxygen free radicals, the pathological basis of early pulmonary edema is alterations in the tight junctions of the alveolar epithelium and capillary endothelium.

Animals↗
PubMed1989

[Observation on the efficacy and experimental study of compound suanzaoren ansen capsules in insomnia].

374 patients suffering from insomnia were divided into three groups by random: 202 cases in group I were treated with compound Suanzaoren Ansen capsules (SAC); 85 cases in group II were treated with Zhusha Ansen pills (ZAP) as control; 87 cases in group III were treated with Methaqualone (Hyminal) also as control. The therapeutic results were as follows: Groups I, II and III showed significant effective rates of 49.50%, 18.82% and 32.18% respectively; moderate effective rates of 34.65%, 48.24% and 49.43% respectively; and total rates of effectiveness of 84.15, 67.06% and 81.61% respectively. The authors found significant statistical difference between group I and II (P less than 0.005) and of no statistical difference between group I and III (P greater than 0.05). The results showed that the effects of compound SAC were better than ZAP, and similar to that of methaqualone. EEG analysis carried out while sleeping confirmed the effects mentioned above. Low toxicity (LD50 10.7 g/kg) of compound SAC was found through animal experimentations. No towards reactions were revealed in clinical trials except nausea in 3 cases. Heart rate and blood pressure changed lightly in a few cases.

Adolescent↗
PubMed1989

Visualization of vascular platelet aggregation by plastic embedding and light microscopy.

Previous studies have indicated that platelets play a role in inflammation and microvascular damage but routine histologic preparations do not permit clear visualization of the platelets in tissues. Plastic embedding was used in this study to demonstrate platelet aggregates in the pulmonary vasculature of mice exposed to complement activation. The degree of platelet aggregation in the excised lungs was graded semiquantitatively in a total of 75 mice. Control Balb/c mice had a mean aggregation score of 0.16 while mice which received 0.3 ml zymosan-activated plasma (ZAP) intravenously (iv) had a score of 2.2. Injection of 0.3 or 0.4 ml of ZAP to which epsilon-aminocaproic acid was added prior to incubation with zymosan resulted in a score of 2.6 or 4.7 respectively. Balb/c (C5 sufficient) and AKR/J (C5 deficient) mice injected iv with 1 mg zymosan had scores of 2.9 and 3.2, respectively. Cobra venom factor (CVF) injected iv to Balb/c mice induced a dose-dependent aggregation. Taken together, these results confirm that complement activation products can mediate intrapulmonary platelet aggregation and they also demonstrate the suitability of plastic embedding for visualization of intravascular platelet aggregates under light microscopy.

Animals↗
PubMed1983

Leukocyte metabolism and function in uremia.

Leukocyte metabolism was studied in 13 non-diabetic hemodialysis patients, 8 clinically stable, nondiabetic transplant recipients, and 13 control subjects. Metabolic parameters included rates of oxygen consumption (nmoles/min/10(6) cells), glucose uptake, lactate production (nmoles/hr/10(6) cells), and 14C-l-glucose oxidation to 14CO2 (nmoles/hr/10(6) cells). Granulocyte metabolism was stimulated by phagocytosis of opsonized zymosan (Z) and by the membrane perturbing agent phorbol myristate acetate (PMA). Granulocyte motility in response to zymosan-activated plasma (ZAP) was also studied. Granulocytes from hemodialysis patients showed significantly impaired stimulated oxygen consumption (Z = 2.41 +/- 0.30 vs. 3.73 +/- 0.39; PMA = 2.63 +/- 0.33 vs. 3.67 +/- 0.19), resting glucose uptake (17.7 +/- 2.9 vs. 36.5 +/- 3.5), stimulated glucose uptake (Z = 44.2 +/- 7.1 vs. 71.8 +/- 5.3; PMA = 63.7 +/- 5.5 vs. 92.8 +/- 5.6), stimulated lactate production (Z = 68.4 +/- 5.1 vs. 97.5 +/- 9.3; PMA = 70.7 +/- 4.9 vs. 92.7 +/- 5.4), and ZAP-stimulated granulocyte motility (16 +/- 3 vs. 30 +/- 4 mu). Metabolic responses of granulocytes from transplant recipients were frequently intermediate between those of hemodialysis patients and controls, but not significantly different from controls. Abnormalities of glucose and oxygen metabolism in granulocytes from uremic patients may cause or contribute to granulocyte dysfunction and vulnerability to infection in such patients.

Adult↗
PubMed1984

Kinetics of neutrophil accumulation in acute inflammatory lesions induced by chemotaxins and chemotaxinigens.

The influx of neutrophils into cutaneous lesions induced with the chemotaxins formylmethionyl-leucyl-phenylalanine (FMLP), platelet-activating factor (PAF), and alpha-casein, and the chemotaxinigens endotoxin and zymosan peaked at 2 to 4 hr and then rapidly declined. In contrast, concanavalin A (Con A) induced a biphasic influx of neutrophils with an initial peak at 2 hr and a subsequent, prolonged peak between 6 and 10 hr. When the kinetics of the neutrophil influx into lesions induced with FMLP at 10(-5) M, 10(-6.5) M and 10(-8) M were examined, it was found that a comparable proportion of the total cell influx entered lesions induced with each concentration of FMLP at each time point. This result indicates that the kinetics of the neutrophil influx into an inflammatory lesion is not dependent on the concentration of chemotaxin within the lesion. The inflammatory potency of FMLP, PAF, alpha-casein, Con A, and endotoxin were compared with leukotriene B4 (LTB4) and zymosan-activated plasma (ZAP) as a source of C5 fragments. Equipotent concentrations were 10(-4) M alpha-casein, 10(-5) M PAF, 10(-5.5) M LTB4 and Con A, 10(-6) M FMLP, 10(-7) M ZAP, and 10(-11) M endotoxin.

Acute Disease↗
PubMed1981

An easy quantitative cytotoxicity assay using a Coulter Counter.

A rapid and reproducible cytotoxicity assay using an electronic particle counter, such as a Coulter Counter, is described. With anti-BAtheta antiserum and mouse thymocytes as target cells, comparable, but more objective results than those by the ordinary dye exclusion method were obtained in a short time. The procedure is very simple: Cells in a plastic multi-well plate are first exposed to antibody and complement or other cytolytic conditions and then Pronase E is added to each well to digest dead cells completely. Then the nuclei of remaining viable cells are liberated from the cytoplasm and cell debris by solubilization with Zap-Oglobin and counted in the counter. Under these conditions, contaminating erythrocytes do not cause interference, because they are completely solubilized with Zap-Oglobin. This technique should be useful for measurements on numerous samples, such as in monitoring chromatograms of cytotoxic activity and titrating antibody and complement.

Animals↗
PubMed1981

Role of chemotactic factor inactivation in neutrophil chemotaxis.

CFIs have been implicated in the regulation of several inflammatory mediators; consequently, we have evaluated the effects of CFI on neutrophil chemotactic and lysosomal enzyme release response to C5-derived chemotaxins. Chemotaxis was measured by direct migration under agarose, LER by glucosaminidase release from cytochalasin B-treated neutrophils, and CFI activity by its inhibition of LER. After inactivation by CFI, C5-fr lost their ability to stimulate neutrophils, and acquired a new chemotactic inhibitory activity. On gel chromatography, the stimulatory activity of C5-fr and the inhibitory activity of inactivated C5-fr eluted as separate peaks with different molecular weights. Effects of CFI on neutrophil responses to C5-fr, ZAS, and ZAP were adverse and dose-dependent: maximal neutrophil response to C5-ft decreased in amplitude as CFI levels increased, and a close reciprocal relationship was demonstrated between the endogenous CFI and the chemotaxis activities of ZAS (r = -0.833) and ZAP (r = -0.932) in 10 healthy adults. The data suggest that CFI is a potent regulator of neutrophil response to C5-derived inflammatory mediators.

Adult↗
PubMed1980

Enhanced vascular permeability and haemorrhage-inducing activity of rabbit C5ades arg: probable role of polymorphonuclear leucocyte lysosomes.

We previously reported that the injection into rabbit skin of rabbit zymosan-activated plasma (ZAP) induces marked polymorphonuclear leucocyte (PMN) infiltration, a transient increase in vascular permeability (1 hr) and prolonged red blood cells extravasation lasting at least 10 hr. Here we describe the fractionation of ZAP to identify the factor(s) responsible for these effects. On CM Sephadex G-25 chromatography, the majority of the leucocyte-attracting, permeability-enhancing and haemorrhage-inducing activities eluted in the high-salt fractions (0 . 6 M ammonium formate, 1 M NaCl pH 5 . 0), suggesting that this is a very basic molecule(s). Furthermore, the three activities eluted in the same fraction on Sephadex G-100, with an apparent molecular weight of 14,000--17,000 daltons. These observations, and the previously described requirement for C5 in the plasma, suggest that C5ades arg is the active factor. Experiments performed in neutropenic rabbits indicated that PMN are required for both the increase in permeability and red cell extravasation. Ultrastructural studies showed extensive degenerative changes in the infiltrating PMNs evident even in 1--2-hr lesions. These ranged from 'watery' cytoplasm, loss of glycogen and cell membrane to segregation and extensive extracellular release of lysosomes. It is postulated that C5ades arg-induced chemotaxis and metabolic perturbations contribute to this rapid degeneration of the PMNs, and that the release of lysosomes from these cells results in progressive vascular injury.

Animals↗