PMN Phagocytosis Research Articles

Effects of lead on polymorphonuclear leukocyte (PMN) functions in occupationally exposed workers.

Previous in vitro experiments have shown that lead can inhibit PMN chemotaxis, phagocytosis and superoxide formation. Moreover, we have observed an inhibition of PMN chemotaxis in workers occupationally exposed to lead with a mean blood lead concentration of 3.06 mumol/l. The present study was carried out to evaluate locomotion and luminol assisted chemiluminescence (CL) of polymorphonuclear leukocytes (PMN) harvested from ten lead occupationally exposed workers with blood lead concentrations of 1.59 mumol/l (SD 0.27 mumol/l). Since lipids affect PMN activity and lipid composition is modified in erythrocytes of lead workers, PMN lipids were also studied. Ten healthy male subjects of the same age were taken as controls. Chemotaxis, i.e. locomotion stimulated through a specific membrane receptor, was impaired in the PMN of lead workers, but random migration, i.e. unstimulated cell locomotion, and respiratory burst were both unmodified. Cholesterol and phospholipids were not changed, but the percentage of arachidonic acid was significantly increased. The release of LTB4, generated by the oxidative metabolism of arachidonic acid, was increased. CL, which detects reactive oxygen species (ROS), was unmodified, but this lack of change could be the result of an increase in ROS, due to the augmentated percentage of arachidonic acid, and of a decrease in ROS, due to a direct inhibitory effect of lead on ROS generation. On the basis of the results from these ex vivo experiments, the conclusion that chemotaxis is the PMN function primarily affected by lead was confirmed. PMN are considered to be one of the first cellular targets for the action of lead; low exposure to lead modifies their activity and mainly modifies chemotaxis and LTB4 production.

The effects of IL-1, IL-2, and tumor necrosis factor on polymorphonuclear leukocyte Fc gamma receptor-mediated phagocytosis. IL-2 down-regulates the effect of tumor necrosis factor.

It has been reported that the Fc gamma R-mediated phagocytic activity of polymorphonuclear leukocytes (PMN) from patients with acute bacterial infections is markedly enhanced when compared with healthy controls. Inasmuch as several potent cytokines are known to be involved in inflammatory and infectious processes, we studied the effects of three such cytokines (IL-1 beta, IL-2, and TNF-alpha) on normal PMN Fc gamma R-mediated phagocytosis. IL-1 beta and TNF alpha both caused a significant increase in the ingestion of EIgG by adherent PMN. In combination, IL-1 beta and TNF-alpha had an additive effect, even when each was used at its optimal concentration. In contrast to the enhancing effects mediated by IL-1 beta and TNF-alpha, IL-2 alone had no significant effect on PMN phagocytosis. Notably, however, IL-2 at a concentration of 10(4) U/ml partially inhibited TNF-alpha-mediated enhancement of phagocytosis by decreasing TNF binding to the PMN cell surface. This inhibitory effect of IL-2 on TNF was reversed by anti-IL-2 antibody and mAb directed against the low affinity IL-2R (anti-Tac), whereas mAb directed against the intermediate affinity receptor (mik-beta 1) had no such effect. These findings may have important physiologic implications, because patients receiving IL-2 therapy have been shown to have increased susceptibility to infection.

Ontogeny of fetal sheep polymorphonuclear leukocyte phagocytosis

Premature infants and neonates are vulnerable to bacterial sepsis. This susceptibility may be due to the relative immaturity of their immune systems. To determine if neonates and, in particular, premature infants have decreased polymorphonuclear leukocyte (PMN) phagocytosis, we tested PMN phagocytosis of Staphylococcus aureus as a function of gestational age in the fetal lamb model. Because phagocytosis is made more efficient by the presence of opsonins in plasma, fetal and postnatal PMN phagocytosis were also measured after exposure to fetal and adult plasma. PMNs were isolated from fetal lambs at 104, 114, 124, and 141 days' gestation (term gestation for the fetal lamb is 145 days), as well as from 10-day-old neonatal sheep and adult sheep. Labeled S aureus were opsonized by incubation in either fetal or adult plasma, or left unopsonized for baseline values. Phagocytosis was measured as a percent of adult PMN phagocytosis after adult plasma opsonization. It was found that fetal PMN function is limited by two factors during the early third trimester: a primary defect in the ability of the PMN to phagocytose S aureaus despite adequate opsonization, and the diminished ability of autologous fetal plasma to opsonize bacteria. The defect in PMN phagocytosis disappears late in the third trimester, but the inability of the fetal plasma to opsonize effectively continues until after birth.

Monokines released during short-term Fc gamma receptor phagocytosis up-regulate polymorphonuclear leukocytes and monocyte-phagocytic function.

Freshly explanted monocytes phagocytosing IgG antibody-coated erythrocyte targets (EIgG) release a factor(s) that stimulates phagocytosis by neighboring monocytes and polymorphonuclear leukocytes (PMN). Culture supernatants obtained after 30-min incubation of adherent monocytes with EIgG, but not unopsonized sheep erythrocytes, markedly up-regulated the extent of PMN phagocytosis and enhanced the rate at which monocytes ingested EIgG. The presence of this factor(s) was first evident in phagocytic studies in which monocytes were prepared by a colloidal silica-based continuous gradient technique (Sepracell-Mn). After introduction of erythrocyte targets, there was a 20- to 30-min delay before initiation of phagocytosis that was not observed with monocytes prepared by the standard Percoll-gradient technique. Experiments suggest that, when compared with monocytes prepared by the Percoll-gradient method, Sepracell-Mn monocytes are closer to a base line state of activation with regard to the expression of Fc gamma RI and the ability to ingest EIgG. The mechanism of PMN upregulation by the monocyte factor(s) was explored. Monocyte supernatants did not induce an increase in the surface expression of PMN Fc gamma RI, II, or III. Neither anti-TNF, anti-IL-2, nor anti-GM-CSF had any significant effect on monocyte supernatant activity. Neutrophil activating protein-1 was not detected by ELISA. In contrast, anti-IL-1 completely blocked the effect of the supernatant on subsequent monocyte phagocytosis, and partially inhibited its effect on PMN phagocytosis. Furthermore, it was shown that RIL-1 as well as TNF markedly enhanced monocyte and PMN ingestion of EIgG. These results suggest that monocytes, after Fc gamma R-mediated phagocytosis, release monokines, including at least IL-1, which enhance the phagocytic function of neighboring PMN and monocytes to augment the host defense process.

Phagocytosis of virulent Porphyromonas gingivalis by human polymorphonuclear leukocytes requires specific immunoglobulin G

No studies to date clearly define the interactions between Porphyromonas gingivalis and human peripheral blood polymorphonuclear leukocytes (PMN), nor has a protective role for antibody to P. gingivalis been defined. Using a fluorochrome phagocytosis microassay, we investigated PMN phagocytosis and killing of P. gingivalis as a function of P. gingivalis-specific antibody. Sera from a nonimmune rabbit and a healthy human subject were not opsonic for virulent P. gingivalis A7436, W83, and HG405; phagocytosis of these strains (but not 33277) required opsonization with hyperimmune antiserum (RaPg). Diluting RaPg with a constant complement source decreased proportionally the number of P. gingivalis A7436 cells phagocytosed per phagocytic PMN. Enriching for the immunoglobulin G fraction of RAPg A7436 enriched for opsonic activity toward A7436. An opsonic evaluation of 18 serum samples from adult periodontitis patients revealed that only 3 adult periodontitis sera of 17 with elevated immunoglobulin G to P. gingivalis A7436 were opsonic for A7436 and, moreover, that the serum sample with the highest enzyme-linked immunosorbent assay titer was most opsonic (patient 1). However, the opsonic activity of serum from patient 1 was qualitatively and not just quantitatively different from that of the nonopsonic human sera (but was less effective opsonin than RaPg). Strain variability was observed in resistance of P. gingivalis to phagocytosis, and opsonization was strain specific for some, but not all, strains tested. An evaluation of killing of A7436 revealed that serum killing and extracellular killing of P. gingivalis were less effective alone when compared with intracellular PMN killing alone.

Neutrophil (PMN) phagocytosis and chemotaxis after 2 hr of ischemia

The role of PMN in the reperfusion injury after ischemia is unclear. It was the purpose of this study to determine if PMN functions of phagocytosis and chemotaxis were altered after a brief period of ischemia (2 hr) followed by reperfusion (1 hr) in a model where no significant reperfusion injury occurred. Baseline blood samples were drawn from an ear artery from New Zealand white rabbits for PMN and serum. The right iliac and femoral arteries were clamped for 2 hr. Just prior to clamp release, blood was harvested from the right iliac vein. After 1 hr of reperfusion, blood was again harvested from the right iliac vein. Phagocytosis was measured by the percentage ingestion of zymosan by PMN. The zymosan beads had been opsonized with baseline (b), ischemia (i), or reperfusion (r) serum. Chemotaxis was evaluated by the number of PMN migrating across a filter. Serum obtained from b, i, and r blood samples served as the chemoattractants. Results for phagocytosis demonstrated a significant increase in i and r PMN as compared to b PMN. Opsonization by b, i, or r serum did not enhance this effect (ANOVA, F = 4.477; P = 0.0266). Similar increases in chemotaxis were observed for i and r PMN which also were not enhanced by the chemoattractants of b, i, or r serum (ANOVA, F = 25.43; P < 0.001). We conclude that (1) rabbit PMN phagocytosis and chemotaxis were increased after both 2 hr of ischemia and 1 hr of reperfusion, (2) this effect was not augmented by i or r serum, and (3) rabbit PMN functions of phagocytosis and chemotaxis were stimulated in this model after a brief period of ischemia and after reperfusion before a clinical reperfusion injury took place.

The effect of sanguinarine on human peripheral blood neutrophil viability and functions

Human polymorphonuclear cell (PMN) viability, morphology, adherence, chemotaxis, oxidative metabolism, degranulation and phagocytosis were evaluated following treatment with sanguinarine (SANG). SANG was noncytotoxic to PMNs at all concentrations tested (0.31-200 microM). SANG entered the PMNs rapidly without altering the membrane fluidity and localized in the nuclear matrix. SANG (1.56-6.21 microM) inhibited chemotaxis, chemokinesis and adhesion in a dose-dependent manner, with a complete inhibition at 6.2 microM concentration. Concentrations of SANG up to 1.56 microM did not affect PMN oxidative burst; however, higher concentrations were found to inhibit basal as well as PMA-induced superoxide anion generation. The effect of SANG was time- and dose-dependent, and could be reversed if the PMNs were exposed to 12.5 microM or lower concentrations of SANG for less than 5 min. Autologous serum increased the tolerance of PMNs to SANG. Exogenous Ca2+ or Mg2+ did not alter the SANG-mediated inhibition of PMN functions. Treatment of PMNs with 3.12 microM or higher concentrations of SANG also resulted in inhibition of PMN degranulation and phagocytosis. The results suggest that SANG-mediated inhibition of PMN functions, without cytolysis or resultant release of inflammatory mediators, may have clinical implications.

Adverse effect of delta 9-tetrahydrocannabinol on human neutrophil function.

Marijuana smoking has been reported to produce a variety of effects on the immune system of man. In 1974, Nahas et al. first described the defect in lympho-proliferative response to alloantigens in chronic marijuana smokers (1). Since then, numerous investigators have pursued studies involving the effects of various cannabinoids from marijuana, including the major psychoactive component, ?9-tetrahydrocannabinol (THC), found in the blood of marijuana smokers. We and others have previously documented that THC impairs lymphocyte responsiveness to mitogens (1–5), alters alveolar macrophage morphology, function, and mobility (6–8), decreases NK activity (9,10) and IFN production (11). However, the effect of cannabinoids on PMN is little known. One report cites the impairment of phagocytosis in PMN of marijuana smokers (12), but no studies to date exist on the direct effect of THC on PMN in vitro. As we have described earlier, PMN provide an effective mechanism against Candida albicans growth, and constitute a key defense system against opportunistic fungal infection (13,15). The likelihood exists that marijuana usage might adversely affect some of the immune mechanisms necessary for control of C. albicans. This could then provide an environment for further immune suppression by HIV in high risk individuals, leading to spread of opportunistic infections. Therefore, there is a need to begin to explore in depth the little-known effect of THC on human PMN and to investigate the effect of THC on defense against an opportunistic microbial agent such as C. albicans.KeywordsPhorbol Myristate AcetateHuman Natural Killer CellMarijuana SmokerMarijuana UsageOpportunistic Fungal InfectionThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

In-vitro effects of teicoplanin, teicoplanin derivative MDL 62211 and vancomycin on human polymorphonuclear cell function

The in-vitro effects on human neutrophil (PMN) functions of three structurally related glycopeptide antibiotics, vancomycin, teicoplanin and the teicoplanin derivative MDL 62211 were investigated. Teicoplanin and MDL 62211 significantly inhibited adherence, chemotaxis, phagocytosis and killing of Candida albicans by PMN's at a concentration of 500 mg/l, whereas PMN viability was only affected at drug concentrations of 2000 mg/l. Vancomycin interfered with PMN adherence and phagocytosis only at a concentration of 2000 mg/l without affecting PMN viability. Chemotaxis and killing of C. albicans were also not affected by this concentration. Teicoplanin and the teicoplanin-derivative MDL 62211 was found to have adverse effects on selected indices of PMN function in vitro only at concentrations higher than those employed in therapy, while vancomycin interfered only at very high concentrations.

Effect of hyperbaric oxygen on murine neutrophil and T-lymphocyte functions

We investigated the effect of repeated hyperbaric oxygen (HBO) exposure on PMN and T-lymphocyte functions in a murine model. Animals received eight 90-min exposures twice daily to 2.4 ata and 100% or 10% oxygen. Control animals were maintained in room air. On the ninth day spleens and peritoneal cell exudates were harvested. Phagocytosis was measured by flow-cytometric analysis of the ability of PMN to engulf formalin-killed, fluorescence-labeled Staphylococcus aureus. PMN-killing capacity was measured by the ability of PMN to undergo an oxidative burst after stimulation with N-formyl methionyl-leucyl-phenylalanine, phorbol myristate, or opsonized zymosan. T-lymphocyte subpopulations were identified using monoclonal antibodies and two-color flow cytometry after 48 h stimulation with phytohemagglutinin, and lymphocyte proliferation was measured by 3 H-thymidine incorporation. We found PMN phagocytosis and oxidative burst were unchanged after HBO treatment. Lymphocyte proliferation was decreased, and an activated population of CD8+ T cells appeared after mitogen stimulation. We conclude that, although PMN function is not affected by prior HBO, lymphocyte proliferation is decreased.

Untreated Intra-abdominal Sepsis: Lack of Synergism between Polymorphonuclear Leukocyte (PMN) Complement Receptors CR1/CR3 and IgG Receptor FcRIII

We have examined the effects of untreated intra-abdominal sepsis on polymorphonuclear leukocyte (PMN) phagocytosis. Phagocytosis was studied in a receptor-specific fashion looking at the interrelationship between FcRIII-, complement receptor (CR1)-, and complement receptor 3 (CR3)-mediated phagocytosis. Twelve swine underwent either sham laparotomy (n = 5) or laparotomy with cecal ligation and incision (n = 7) to induce intra-abdominal sepsis. PMN phagocytosis was assayed on POD 1, 4, and 8. In animals undergoing sham laparotomy, FcRIII-mediated phagocytosis was less than 10% on all days and was augmented with the addition of C3b or C3bi to the target particles (FcR + CR1 or FcR + CR3 greater than FcR alone). In animals undergoing cecal ligation and incision, baseline FcRIII-mediated phagocytosis increased between POD 1 and 4 and fell between POD 4 and 8. No increase in phagocytosis was seen on POD 4 or 8 with the addition of C3b or C3bi to the target particles (FcR + CR1 or FcR + CR3 = FcR alone). Preligation of the FcRIII but not FcRII or FcRI receptor with a monoclonal antibody (3G8) markedly reduced phagocytosis in the animals with intraabdominal sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of Membranes on Generation of β2 M and Release of Leukocyte Lysosomal Enzymes

Normal leukocyte functional capacity was investigated by evaluation of phagocytosis of opsonised yeast cells in a radiometric test system. After incubation with dialysis membranes (different cellulosic membranes, polysulfon membrane (PS), polymethylmetacrylate membrane (PMMN), the phagocytosis index, expressed as percent decrease with respect to initial values without membrane, decreased by 10%-25%. The most pronounced effect was observed with PS, cuprophane, modified cellulose and PMMA. The results are not related to differences in the viability of PMN during the test procedure; dead PMN amounted to about 4-6.5%. A significant increase in beta-NAG and beta-Gluc activities was released in the supernatants of the phagocytosis suspensions. This increase activity can be explained by the phagocytosis of PMN but it was not influenced by membrane contact. There was no influence of membrane contact or phagocytosis activity of PMN on the beta 2 M concentration in the supernatant demonstrating that no in vitro generation during incubation with either membrane exists.

Phagocytosis of herpes simplex virus by human granulocytes and monocytes

Polymorphonuclear leukocytes (PMN) can mediate cytotoxic reactions against virus infected targets cells. We observed very efficient binding of PMN to HSV-infected fibroblasts when loaded with HSV-specific antibodies. Using electron microscopy, infected fibroblasts were found to be totally surrounded by PMN and the phagocytosis of virions and fragments of infected cells was demonstrated. To quantify and study this phenomenon, and to compare PMN with monocytes, we developed radiometric and fluorometric phagocytosis assays. Leukocytes were mixed with [3H]glucosamine- or FITC-labeled virus and incubated at 37 degrees C. PMN associated radioactivity or fluorescence per cell as measured by flow cytometry was determined. PMN phagocytosis was dependent on the presence of specific anti-HSV antibodies and could be enhanced by addition of complement. Monocytes were also able to phagocytize virions; however, the rate of uptake was less than that for PMN. Under optimal conditions the total amount of herpes simplex particles that could be associated with one PMN or monocyte was about 10,000. PMN and monocytes are capable of phagocytosis of HSV. This may be an important factor in preventing the spread of infection in vivo.

Inflammatory cell function in young rodents with experimental cholestasis: Investigations of functional deficits, their etiology, and their reversibility

Children with cholestasis are susceptible to infective complications. This may be attributable to impaired host defense. We postulated that cholestasis affects systemic polymorphonuclear leukocyte (PMN) function by impeding chemotaxis, phagocytosis, and superoxide release, which are all critical in eliciting an adequate immune response. Sprague Dawley rats (225 g) were assigned to three groups: bile duct ligated (BDL), sham (SH), and normal control (NC). On day 21 after operation, PMN and sera were isolated. Chemotactic response to C5a and FMLP (formyl-methionyl-leucyl-phenylalanine), superoxide release, and phagocytic uptake of 14C-labeled Staphylococcus aureus were performed on pooled PMN samples. Results were expressed as mean +/- SD. Serum bilirubin at day 21 was 6.3 +/- 2.9 v 0.1 +/- 0.1 and 0.1 +/- 0 mg/dL (P less than .01) in BDL, SH, and NC groups, respectively. Kinetic studies of PMN phagocytosis demonstrated impaired 14C S aureus uptake by BDL neutrophils at 60 (P less than .05), 90 (P less than .05), and 120 minutes (P less than .05) compared with SH and NC groups. No differences in PMN chemotactic response to C5a and FMLP was observed in BDL, SH and NC groups (43 +/- 14 v 40 +/- 12 and 33 +/- 1, and 43 +/- 20 v 43 +/- 14 and 28 +/- 1 cell per field, respectively). Zymosan stimulated superoxide release did not differ between groups (14.3 +/- 3.6 (BDL) v 15.1 +/- 8.7 (SH) and 12 +/- 2.0 (NC) nmol/30 min/mg cell protein, respectively. Thus, cholestasis impairs neutrophil phagocytosis in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of tumor necrosis factor-α and interferon-γ on neutrophil function

Tumor necrosis factor-α (TNF) and interferon-γ (IFN-γ) have been shown to regulate cell-mediated immunity and act as effective modifiers of immune function; however, their influence on neutrophil (PMN) function is not well defined. This study investigated the effect of these cytokines on PMN phagocytosis, respiratory burst, and complement receptor (C3b) expression. Human citrated whole blood was incubated with either phosphate-buffered saline (control), 20 μg Escherichia coli lipopolysaccharide (LPS), TNF (1, 10, or 100 units), or IFN-γ (1, 10, or 100 units). Synergy was also assessed between TNF and IFN-γ. Phagocytosis and respiratory burst were assayed by sequential incubation of blood with dichlorofluorescin diacetate followed by labeled Staphylococcus aureus. C3b receptor expression was assayed by labeled anti-CR3 monoclonal antibody. Measurements were expressed as the mean channel fluorescence of 2000 PMNs counted by flow cytometry. IFN-γ alone at all doses had no effect on any of the parameters measured. TNF 1 unit/ml increased phagocytosis (666 ± 47 vs 542 ± 19), respiratory burst (326 ± 33 vs 258 ± 17), and C3b (374 ± 42 vs 157 ± 14; all P < 0.05) over those of control. TNF also demonstrated dose-dependent PMN activation. The combination of TNF + IFN-γ increased both respiratory burst and C3b compared to either agent alone. These data indicate that TNF enhances PMN function and cytokine interaction may be important in PMN activation.

Neutrophil phagocytosis during endotoxin-induced lung injury

Depressed neutrophil (PMN) phagocytosis in patients with ARDS may contribute to the known increased incidence of pulmonary sepsis. To evaluate changes in phagocytosis, circulating PMNs from normal rats were compared to circulating and alveolar PMNs (obtained by bronchoalveolar lavage, BAL) from rats after 72 hr of endotoxin infusion (LPS-Rx)-induced acute lung injury. Since phagocytosis correlates with adherence, PMN adherence to coverslips and to a standard nylon wool column was also measured. PMN adherence to nylon wool was 65% for control, 77% for circulating LPS-Rx, and 20% for BAL PMNs. As a measure of phagocytosis the PMNs were incubated for 30 min with opsonized fluorescent (FITC) tagged yeast. Total PMN with yeast were 95.4 ± 2.1% for control; 96.4 ± 1.8% for circulating LPS-Rx; and 78.7 ± 7.8% ( P < 0.05 compared to control) for BAL PMNs. Total numbers of yeast particles per 100 PMN are 270 ± 64 for control, 300 ± 42 for circulating LPS-Rx, and 170 ± 45 ( P < 0.05 compared to control) for BAL PMN. Conclusions: (1) Intraalveolar (BAL) PMNs have decreased adherence; (2) nonadherent PMNs have decreased uptake of yeast; (3) BAL PMNs, overall, have a significantly decreased uptake of yeast; (4) this depression in BAL PMN phagocytosis may partially explain the known decreased rate of bacterial clearance in injured lungs and the increased risk of pulmonary sepsis with adult respiratory distress syndrome.

Suppression of human polymorphonuclear leukocyte phagocytosis by adenosine analogs.

The effects of adenosine analogs on human polymorphonuclear leukocyte (PMN) phagocytosis to latex beads or sheep red blood cells were investigated in an in vitro experiment. The purine compounds such as N6-phenylisopropyladenosine (PIA), 5'-N-ethylcarboxamido-adenosine (NECA), an A2 adenosine receptor agonist, and adenosine as high as 2 mM had no effect on PMN phagocytosis. In contrast, 2',5'-dideoxyadenosine (DDA), a P-site adenosine receptor agonist, and 5'-methylthioadenosine (MTA), a naturally occurring purine nucleoside, caused profound inhibition of phagocytic function of PMNs in a dose-dependent manner. Dipyridamole, which blocks purine nucleoside uptake, reversed the suppression due to MTA. Theophylline, an R-site receptor antagonists did not prevent the effect of MTA. These results suggested that phagocytosis of PMNs is suppressed by stimulation of the P-site adenosine receptors.

Mechanism by which methylprednisolone inhibits acute immune complex-induced changes in vascular permeability.

Intravital microscopy was used to quantitate protein leakage which resulted from the deposition of immune complexes in the vasculature of the rat cremaster muscle. Immune complex deposition was initiated by the addition of 80 micrograms/ml of ovalbumin to the bath surrounding the muscle, followed by the intravenous administration of antiovalbumin. Administration of 25 mg/kg of antiovalbumin produced significant leakage of protein from the third-order venules, while 7.5 and 2.5 mg/kg had no effect. Administration of methylprednisolone (MP), 30 mg/kg, 1 h prior to the deposition of immune complexes significantly inhibited protein leakage. In separate experiments, MP inhibited intradermal edema formation and protein exudation induced in rats by histamine, platelet activating factor, or C5a. However, MP had no effect on protein exudation or edema produced by xanthine oxidase or glucose oxidase. Intravenous administration of MP inhibited the ability of polymorphonuclear leukocytes (PMNs) to phagocytize bacteria, but failed to alter hydrogen peroxide production. These results suggest that MP prevents acute changes in vascular permeability following immune complex deposition by inhibiting the effects of soluble mediators of edema on vascular endothelium and by inhibiting PMN phagocytosis.

Peripheral blood phagocyte function in acute necrotizing ulcerative gingivitis

Eleven patients suffering from acute necrotizing ulcerative gingivitis (ANUG) and 11 healthy controls, were analyzed for: 1) peripheral blood polymorphonuclear leukocyte (PMN) chemotaxis; 2) monocyte chemotaxis; 3) PMN phagocytosis; and 4) PMN intracellular killing A modification of the Boyden chamber technique was developed to determine in vitro cellular migration in test and control groups. Nitroblue tetrazolium (NBT) reduction and a candidacidal assay were used to investigate PMN phagocytosis and intracellular killing. Ten of the patients with ANUG were found to have depressed PMN chemotaxis. The difference, compared to control subjects, was significant at the 95% confidence level. The impaired chemotaxis of PMN was due to an intrinsic defect in the cells themselves, as abnormal levels of cell‐directed chemotactic inhibitors, inactivators of chemoattractants, or complement‐derived chemoattractants were not demonstrated in the serum of the patients with ANUG. Monocyte chemotaxis was enhanced in one of the ANUG patients. No differences were found between ANUG patients and controls in PMN reduction of NBT and intracellular killing. Four of the 11 ANUG patients were re‐examined 18 months later, when they were free of the symptoms of ANUG. None of the subjects demonstrated impaired neutrophil chemotaxis at this point, indicating that the defect may be a transient one associated in time with the ANUG episode.

Comparison of blood and peritoneal neutrophil activity in rabbits with and without peritonitis

The neutrophil (polymorphonuclear cell, or PMN) function is an essential component of the host defense against infection. However, infection itself may alter PMN activity. To investigate both the effects of infection on PMN activity and PMN activity on survival, we evaluated control and infected blood and peritoneal PMN phagocytosis, chemotaxis, and superoxide anion production in rabbits with and without peritonitis. Control blood and peritoneal PMNs were obtained from noninfected rabbits which were subjected to intraperitoneal infusion of sterile hypertonic saline. Infected blood and peritoneal PMNs were obtained from rabbits which had undergone appendiceal devascularization and ligation 18 hr earlier. Phagocytosis was similar in all groups except for a threefold increase in normal peritoneal PMNs. Chemotaxis was inhibited by infection in the blood and peritoneal PMNs. Normal peritoneal PMNs also had decreased chemotaxis. Superoxide anion production was comparable in the infected and control blood; however, both control and infected peritoneal PMNs had elevated superoxide anion production. Of the infected rabbits, four died in 5 days or less. Of the six that lived, two developed intraabdominal abscesses. Blood and peritoneal PMN activity was similar in all rabbits despite their outcome. We conclude that (1) blood and peritoneal PMNs have different basal activities and responses to infection; (2) the milieu of the peritoneal cavity appears to alter the PMNs present; and (3) PMN activity did not predict morbidity or mortality.