Biomedical subjects

H H Simms

Publications and source records attributed to H H Simms.

54 records · Page 3Linked to original sources

PubMed1994

Regulation of whole blood polymorphonuclear leukocyte phagocytosis following hypoxemia and hypoxemia/reoxygenation.

Phagocytosis of whole blood polymorphonuclear leukocytes (PMN) was evaluated following periods of hypoxemia or hypoxemia/reoxygenation. Hypoxemia (O2 saturation 5-20%) significantly increased the percentage of PMN positive for phagocytosis. This effect required mobilization of intracellular Ca2+ stores and was accompanied by a significant increase in CD16, CD32w, and CD35 expression assayed using FITC-labeled Mabs. PMA (10 ng/ml) increased CD32w expression while protein kinase C inhibitors H-7 and staurosporine but not the protein kinase A inhibitor H-9 reversed the effect of hypoxemia on phagocytosis and receptor expression. Further, genistein (tyronsine kinase inhibition) reversed hypoxemia-induced increases in phagocytosis (ID50-50 microM). Reoxygenation (O2 saturation 97-99%) reduced the percentage of PMN positive for phagocytosis back to baseline values without affecting mean channel fluorescence. Reoxygenation reduced CD32w and CD16 expression with kinetics assays demonstrating concordance between reduced phagocytosis and CD32w and CD16 expression. Reoxygenation-induced decreases in CD32w and CD16 expression were prevented if whole blood PMN were incubated with either NaN3 (10 mM), dimethyl sulfoxide (DMSO) (10 mM), or taurine (15 mM) prior to reoxygenation. These results demonstrated that hypoxemia and hypoxemia/reoxygenation recruit and suppress distinct populations of whole blood PMN for phagocytosis. Intracellular kinase activation and Ca2+ mobilization are required for hypoxemia-induced increases in phagocytosis. Reoxygenation reduces whole blood PMN phagocytosis via an oxident-derived reduction of surface CD16 and CD32w expression.

Calcium↗

PubMed1994

Hypoxemia regulates effect of lipopolysaccharide on polymorphonuclear leukocyte CD11b/CD18 expression.

Expression of the receptor CD11b/CD18 on the polymorphonuclear leukocyte (PMN) surface is important for several aspects of PMN function during endotoxemia. The mechanisms underlying regulation of CD11b/CD18 expression during hypoxemia and endotoxemia, however, are less clear. We investigated the effects of exposure of whole blood PMNs to lipopolysaccharide (LPS) during hypoxemia. During hypoxemia (10-30% O2 saturation), LPS reduced CD11b/CD18 expression. Both kinetic assays and experiments with microfilament stabilizers (phalloidin, cytochalasin B) demonstrated that this was most likely due to receptor shedding. Incubation of whole blood PMNs with an anti-CD14 monoclonal antibody (MEM18) largely prevented the LPS-induced reduction of CD11b/CD18 expression. Decreased CD11b/CD18 expression reduced PMN functional capability, as the binding of its ligand (erythrocytes opsonized with the 3rd component of complement Cbi) and intracellular H2O2 production were reduced. After exposure to LPS, N-formyl-methionyl-leucyl-phenylalanine could rapidly induce new CD11b/CD18 receptors to the cell surface, and this was not inhibited by actinomycin D or cycloheximide. After reoxygenation (> 90% O2 saturation), CD11b/CD18 expression was restored, and this was abrogated by exposure to cytochalasin B. Lipid A was able to reproduce the effects of LPS during hypoxemia and hypoxemia-reoxygenation but required a 10-fold greater concentration to do so. These results demonstrate that during hypoxemia an important pathophysiological property of LPS is to reduce CD11b/CD18 expression. This results in diminished PMN functional capability, which would contribute to the pathogenicity of LPS during acute infectious states.

Antibodies, Monoclonal↗

PubMed1994

Granulocyte colony-stimulating factor reverses septic shock-induced polymorphonuclear leukocyte dysfunction.

BACKGROUND: Polymorphonuclear leukocyte (PMN) function is dependent on normal Fcg receptor expression. Fibronectin and laminin are each capable of modulating the surface expression of CD32w (Fc gamma RII) and CD16 (Fc gamma RIII). Their ability to alter CD64 (Fc gamma RI) expression, however, was unclear; therefore the purpose of these studies was to define the role of CD64 (Fc gamma RI) in modulating PMN oxidative metabolism and degranulation for PMNs adherent to either fibronectin or laminin. METHODS: Experiments were performed in two phases; initially, PMNs isolated from normal volunteers and adherent to buffer, fibronectin, or laminin were studied. Subsequently, two groups of patients were evaluated; group 1 (n = 8) represents control patients undergoing major intraabdominal procedures. Group 2 (n = 12) represents patients in septic shock from defined sources of intraabdominal infection. Monomeric immunoglobulin G was used as a specific ligand for CD64 followed by measurements of superoxide anion, hypochlorous acid, and N-acetyl-beta-glucosaminidase production to measure oxidative metabolism and azurophilic granule degranulation. Six cytokines were then tested to determine their ability to restore biologically active CD64 on group 2 PMNs. RESULTS: Fibronectin or laminin increased CD64 on PMNs of normal volunteers and group 1 patients. CD64 signal transduction augmented superoxide anion, hypochlorous acid, and N-acetyl-beta-glucosaminidase production by PMNs of volunteers and group 1. Neither fibronectin nor laminin increased CD64 expression on group 2 PMNs. Granulocyte colony-stimulating factor restored both receptor number of CD64 and biologic activity of these receptors on the surface of group 2 PMNs in the presence of fibronectin or laminin. CONCLUSIONS: Septic shock depresses CD64 expression on the PMN surface. Restoration of this receptor by granulocyte colony-stimulating factor not only augments receptor number but also improves oxidative metabolism and primary granule degranulation in the presence of either fibronectin or laminin.

Aged↗

PubMed1994

Gastric alkalinization does not increase the risk of pneumonia in critically ill patients.

Nosocomial pneumonia remains an important determinant of hospital-acquired morbidity and mortality. Although therapy designed to prevent stress-induced gastritis has been effective at relieving upper gastrointestinal (GI) bleeding, the use of agents (histamine-2 receptor antagonists, antacids) that raise gastric pH have also been implicated as increasing the incidence of nosocomial pneumonia. Examination of two recently published meta-analyses investigating the role of gastric pH and nosocomial pneumonia and several individual studies show that raising gastric pH does not increase the incidence of nosocomial pneumonia. Importantly, those clinical trials that purport to show that raising gastric pH increases the incidence of nosocomial pneumonia have not been blinded studies and have failed to control for sites of enteral feeding and volume. Taken together, analysis of several clinical trials finds no compelling evidence for the concept that gastric alkalization increases the evidence of nosocomial pneumonia. Given the methodological flaws incurred in several previous studies, the optimal approach for preventing nosocomial pneumonia while preventing stress gastritis-induced upper (GI) bleeding remains to be identified.

Antacids↗

PubMed1993

Hypoxia induces an opsonic mismatch on the polymorphonuclear leukocyte surface-reversal via Arg-Gly-Asp-Ser-mediated adhesion.

Hypoxia remains an important clinical problem and affects neutrophil oxygen-dependent microbicidal pathways. For adequate PMN-cidal activity to occur, two sets of opsonic receptors (FcR, CD16, CD32w; complement receptors, CD35, CD11b/CD18) must be expressed on the cell surface. We hypothesized that hypoxia would adversely affect receptor expression and that the biological surface that the PMN were adhered to would modulate the effect of hypoxia on these receptors. PMN were adhered in the presence of buffer, fibronectin, Arg-Gly-Asp-Ser (RGDS), or laminin followed by assessment of PMN FcR and complement receptors using 125I-labeled monoclonal antibodies directed against these receptors. Hypoxia reduced PMN CD16 and CD32w but not CD35 and CD11b/CD18 expression. Decreasing buffer pO2 led to corresponding decreases in CD16 and CD32w expression. RGDS but not fibronectin or laminin restored CD16 and CD32w expression in the presence of hypoxia. Monensin but not cycloheximide inhibited RGDS restoration of CD16 and CD32w. (cpm bound: CD16, 958 +/- 123 vs 1602 +/- 193; CD32w, 1481 +/- 173 vs 2215 +/- 382 for hypoxia buffer+RGDS +/- monensin.) These results demonstrate that: (1) acute hypoxia creates an opsonic mismatch by reducing CD16 and CD32w without affecting complement receptors CR1 and CR3 (CD35, CD11b/CD18); (2) matrix proteins modulate the effect of acute hypoxia on PMN FcR; (3) the RGDS-binding epitope of fibronectin significantly restores PMN FcR in the face of acute hypoxia; and (4) RGDS upregulates FcR expression during acute hypoxia by increasing receptor recycling to the cell surface.

Cell Adhesion↗

PubMed1992

Hypocalcemia during sepsis. Relationship to resuscitation and hemodynamics.

The ionized calcium (IC) and parathyroid hormone response to polymicrobial intra-abdominal sepsis and the relationship between IC and hemodynamic alterations with and without crystalloid resuscitation were investigated. Thirty swine underwent cecal ligation and incision (n = 19) or sham laparotomy (n = 11), with seven animals that had cecal ligation and incision administered Ringer's solution (50 mL/kg) after each set of measurements recorded on days 0, 1, 2, 4, and 8. An early decrease in mean arterial pressure and cardiac index in animals that had cecal ligation and incision reversed with resuscitation. The IC also fell early and parathyroid hormone level increased in both the unresuscitated and resuscitated septic groups. However, correlation coefficients of mean arterial pressure and cardiac index with IC ranged from .034 to .287 in the septic animals and were lower in the group that had sham laparotomy. We conclude that polymicrobial intra-abdominal sepsis results in decreased IC and an elevated parathyroid hormone level. Hemodynamics do not correlate with IC levels, and resuscitation can be achieved without calcium administration.

Animals↗

PubMed1992

Endotoxin suppresses matrix protein-induced upregulation of PMN candicidal activity: an effect reversed by low-dose TNF-alpha.

We investigated the relationship of polymorphonuclear leukocyte (PMN) candicidal activity, matrix proteins, and lipopolysaccharide (LPS) to determine how LPS modulates the normal enhancing effect of matrix proteins on PMN candicidal activity. LPS reduced PMN candicidal activity when PMN were adhered in the presence of either fibronectin or laminin. In the presence of fibronectin or laminin, LPS reduced CD11b/CD18 expression (the fibronectin receptor) as assessed using sheep erythrocytes coated with C3bi. Experiments with 125I-fibronectin and 125I-RGDS (Arg-Gly-Asp-Ser) demonstrated that LPS reduced both the binding of fibronectin and the bioavailability of the binding epitope on the PMN surface. Stimulating the PMN oxidative burst with PMA but not FMLP also reduced fibronectin and RGDS binding. Incubation of LPS-treated PMN with staurosporine blocked the decrease in fibronectin and RGDS binding. Exposure of PMN to LPS plus low-dose TNF-alpha restored both fibronectin and RGDS binding with a concomitant increase in CD11b/CD18 surface expression. Low-dose TNF-alpha restored PMN candicidal activity in the presence of LPS and was most effective if PMN were preadhered to fibronectin. These results demonstrate that: (1) matrix proteins enhance normal PMN candicidal activity, (2) LPS reduces PMN candicidal activity in the presence of matrix proteins, (3) stimulation of the PMN oxidative burst in particular via protein kinase c activation reduces the bioavailability of the fibronectin receptor, and (4) low-dose TNF-alpha may restore PMN candicidal activity in part by upregulating the surface receptor for fibronectin binding.

Candida albicans↗

PubMed1992

Intra-abdominal sepsis alters tumor necrosis factor-alpha and interleukin-1 beta binding to human neutrophils.

OBJECTIVE: To determine the effects of intraabdominal sepsis on polymorphonuclear leukocyte tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) receptor expression. DESIGN: Prospective, randomized comparison between patients undergoing elective colon surgery vs. patients with intra-abdominal sepsis. SETTING: Tertiary-care center with all patients with intra-abdominal sepsis in a surgical ICU environment. PATIENTS: Group 1 (n = 7) represents control patients who underwent elective colon surgery without intra-abdominal sepsis. Group 2 (n = 10) represents patients with intra-abdominal sepsis. MEASUREMENTS AND MAIN RESULTS: Polymorphonuclear leukocyte TNF-alpha and IL-1 beta receptor expression +/- stimulation of the oxidative burst was measured using 125I TNF-alpha and 125I IL-1 beta. Superoxide anion production and candicidal activity were measured in the presence of TNF-alpha and IL-1 beta. Group 2 patients expressed fewer TNF-alpha and IL-1 beta receptors on their cell surface, and stimulation of oxidative burst reduced TNF-alpha and IL-1 beta receptor expression in group 2 more than in group 1. Diminished TNF-alpha and IL-1 beta binding reduced superoxide anion production by group 2 polymorphonuclear leukocytes. Decreased TNF-alpha binding but not IL-1 beta, reduced polymorphonuclear leukocyte candicidal activity by group 2 polymorphonuclear leukocytes. CONCLUSIONS: a) Intra-abdominal sepsis reduces polymorphonuclear leukocyte TNF-alpha and IL-1 beta receptor expression. b) Expression of these surface receptors is altered by stimulation of the polymorphonuclear leukocyte oxidative burst. c) Diminished TNF-alpha and IL-1 beta receptor expression is associated with functional impairments in polymorphonuclear leukocyte activity.

Abdomen↗

PubMed1992

Polymicrobial sepsis disrupts normal neutrophil extracellular matrix protein interactions.

The purpose of this study was to examine how intra-abdominal sepsis and extracellular matrix proteins (fibronectin, laminin) affect adherent polymorphonuclear leukocyte (PMN) function. Two groups of swine were studied: Group I (n = 5) underwent sham laparotomy; Group II (n = 8) underwent cecal ligation and incision. PMN adherent to either fibronectin (F) or laminin (L) had increased candicidal activity over buffer (B) by Group I but not by post-operative day 8 Group II PMN. (Percent specific release 51Cr-Group I--35.00, 68.25, 64.75% for B, F, and L; P less than 0.001 comparing B vs. F or L; Group II--14.25, 12.50, 12.75% for B, F, and L; P = NS comparing B vs. F or L.) To determine the mechanism for this finding, PMN priming was then assessed by evaluating both PMN adherence to extracellular matrix proteins and the cell surface expression of CR1/CR3 by using sheep RBC opsonized with C3b or C3bi. PMN activation was assayed by using MTT-Formazan, myeloperoxidase, and hypochlorous acid (HOCl) production. Fibronectin and laminin increased PMN adherence and CR1/CR3 expression over buffer by Group I and Group II animals. Fibronectin and laminin increased MTT-Formazan, myeloperoxidase, and HOCl production over buffer by Group I PMN but not POD 8 Group II PMN. These results suggest that untreated intra-abdominal sepsis partially abrogates the effect of extracellular matrix proteins on PMN function; in particular, the activation but not priming of adherent PMN by extracellular matrix proteins is reduced in this clinical situation.

Animals↗

PubMed1991

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.

Antibodies, Monoclonal↗

PubMed1991

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.

Antigens, Differentiation↗

PubMed1991

Increased PMN CD11b/CD18 expression following post-traumatic ARDS.

We investigated the role of polymorphonuclear leukocytes (PMN) in the pathogenesis of post-traumatic adult respiratory distress syndrome (ARDS). Two groups of patients were studied: Group I (n = 29) represents trauma patients studied within 24 hr of admission to the SICU, and Group II (n = 10) represents a subset of Group I patients who subsequently developed ARDS. Circulating pulmonary artery PMN were then assayed for CD11b/CD18 expression, MTT-Formazan production, intracellular H2O2 production, and superoxide anion release. PMN from Group II patients were upregulated with regard to all of the PMN functions assayed within 24 hr of the diagnosis of ARDS being made. Subsequently, longitudinal assays were performed on 17 patients at risk for the development of ARDS. In 6 of 7 patients prior to the clinical recognition of ARDS, CD11b/CD18 expression and MTT-Formazan production increased significantly over baseline. These results suggest that: (i) ARDS coincides with increased CD11b/CD18 expression on PMN cell surfaces, (ii) PMN oxidative metabolism increases at the onset of ARDS, and (iii) changes in circulating pulmonary artery PMN may provide markers for the development of ARDS in the traumatized patient.

Antigens, CD↗

PubMed1991

Intraabdominal sepsis: enhanced autooxidative effect on polymorphonuclear leukocyte cell surface receptor expression.

We investigated the effects of untreated intraabdominal sepsis on the interrelationship between PMN oxidative metabolism and cell surface receptor expression. Female swine underwent either sham laparotomy (n = 7) or cecal ligation and incision (n = 9) with assays conducted on postoperative days (POD) 0, 1, 4, and 8. Superoxide anion production, intracellular H2O2 production, and the cell surface expression of Fc gamma RII, III, CR1, and CR3 were measured. In addition, phagocytosis of serum-opsonized zymosan was used as a multivalent ligand for CR3 and subsequently Fc gamma RII, III, and CR1 expression were assayed to determine if intraabdominal sepsis induces a linkage between complement and Fc gamma receptor expression. Superoxide anion production increased between POD 0 and 4 and fell between POD 4 and 8 in animals with untreated intraabdominal sepsis. Intracellular H2O2 production rose between POD 0 and 1 and then fell progressively in animals with untreated intraabdominal sepsis. Simulation of the oxidative burst using glucose/glucose oxidase reduced Fc gamma RII and III expression in both sets of animals with a greater reduction seen by POD 4 in animals with intraabdominal sepsis. CR1/CR3 expression was increased with glucose/glucose oxidase by POD 4 in the presence of intraabdominal sepsis. Xanthine/xanthine oxidase did not alter cell surface receptor expression. Phagocytosis of serum-opsonized zymosan decreased subsequent Fc gamma RII expression in animals with intraabdominal sepsis by POD 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗

PubMed1991

Altered polymorphonuclear leukocyte Fc gamma R expression contributes to decreased candicidal activity during intraabdominal sepsis.

We investigated the effects of untreated intraabdominal sepsis on polymorphonuclear leukocyte (PMN) candicidal activity. Two groups of swine were studied. Group I (n = 6) underwent sham laparotomy, group II (n = 7) underwent cecal ligation and incision. Untreated intraabdominal sepsis resulted in a progressive decrease in PMN candicidal activity. Concomitant rosetting and phagocytosis assays demonstrated a decrease in both the attachment and phagocytosis of Candida albicans opsonized with both normal and septic swine serum by PMNs in group II. Iodine 125-labeled swine immunoglobulin G (IgG) and fluorescein isothioalanate (FITC)-labeled swine IgG were used to investigate Fc gamma receptor ligand interactions. Scatchard analyses demonstrated a progressive decline in both the binding affinity constant and number of IgG molecules bound per PMN. Stimulation of the oxidative burst markedly reduced 125I-labeled IgG binding in both group I and group II, with a greater decrement being seen in animals with intraabdominal sepsis. Further, in group II, PMN recycling of the Fc gamma receptor to the cell surface after generation of the oxidative burst was reduced by postoperative day 4. Binding of monoclonal antibodies to Fc gamma receptor II, but not Fc gamma receptor I/III markedly reduced intracellular candicidal activity. Immunofluorescence studies revealed a homogeneous pattern of FITC-IgG uptake by nearly all group I PMNs, whereas by postoperative day 8 a substantial number of PMNs from group II failed to internalize the FITC-IgG. These studies suggest that untreated intraabdominal sepsis reduces PMN candicidal activity and that this is due, in part, to altered PMN Fc gamma receptor ligand interactions.

Abdomen↗

PubMed1991

Role of gastric colonization in the development of pneumonia in critically ill trauma patients: results of a prospective randomized trial.

Critically ill trauma patients were entered in a prospective, randomized trial to determine the role of gastric colonization in the development of pneumonia. Trauma patients admitted to the SICU were randomized to receive antacids (n = 27), continuous IV cimetidine (n = 32), or sucralfate (n = 30). Quantitative nasogastric tube (NGT) cultures were obtained biweekly and correlated with gastric pH, the incidence of pneumonia, and the incidence of pneumonia caused by an organism previously isolated from the stomach (percentage of gastric source of pneumonia--% GSP). Patients receiving antacids had a significantly greater pH than those receiving cimetidine (5.6 +/- 1.03 vs. 4.7 +/- 1.03; p = 0.006). However, there was no significant difference between the overall incidence of pneumonia, the percentage of NGT isolates greater than 10(6)/ml, or the % GSP. The gastric bacteriology of the three subgroups was nearly identical, with Candida albicans, Enterococci, and beta-hemolytic Streptococci being the most frequently isolated organisms. Gastric growth of organisms preceding their appearance in the blood occurred in 5 of 89 (5.6%) patients. These results suggest that 1) in trauma patients, the incidence of pneumonia is not increased by the use of stress ulcer prophylactic agents that elevate gastric pH; 2) increases in gastric pH progressively increased the number of intragastric bacteria but this did not correlate with an increased incidence of % GSP; and 3) while organisms in the upper intestinal tract may be pathogens for pneumonia, they are uncommonly a source of bacteremia in seriously injured patients.

Adolescent↗

PubMed1990

Intraabdominal sepsis: effects on polymorphonuclear leukocyte Fc receptor-mediated phagocytosis.

In vitro studies have shown that phagocytic cells are capable of undergoing activation in response to inflammatory signals and that the activation process is quite complex. A relationship between polymorphonuclear leukocyte (PMN) Fc receptor-mediated phagocytosis and oxidative metabolism has been seen in humans. We have sequentially examined circulating polymorphonuclear leukocytes (PMNs) from a total of 13 postoperative swine with either no sepsis, untreated intraabdominal sepsis, or treated intraabdominal sepsis to determine phagocytic activity over 8 postoperative days (POD). Products of the oxidative burst (i.e., myeloperoxidase) reduced the phagocytic activity of nonseptic swine PMN. Phagocytic activity was augmented by inhibiting the nonseptic swine oxidative burst with 10 mM sodium azide (an inhibitor of myeloperoxidase). In swine with untreated intraabdominal sepsis, PMN Fc receptor-mediated phagocytosis exhibited a biphasic response. An initial (between POD1 and POD4) increase in PMN function was followed by a subsequent (between POD4 and POD8) decrease in PMN function. Partial preservation of phagocytic capability was seen when swine were reexplored on POD4 and had their intraabdominal sepsis treated. These results indicate that (1) as in humans, nonseptic swine PMN Fc receptor-mediated phagocytosis is augmented by inhibition of the PMN respiratory burst; (2) untreated intraabdominal sepsis produces an initial increase and subsequent decrease in PMN Fc receptor-mediated phagocytosis; (3) early treatment of intraabdominal sepsis results in partial restoration of PMN Fc receptor-mediated phagocytosis.

Abdomen↗

PubMed1990

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)

Abscess↗

PubMed1989

Studies on phagocytosis in patients with acute bacterial infections.

Polymorphonuclear leukocytes (PMN) and monocytes from 20 patients with acute bacterial infections were examined for phagocytic function. PMN of patients expressed markedly enhanced phagocytosis as measured by the ingestion of erythrocyte (E)IgG and IgG/C3b-coated E. Phagocytosis of E coated with C3b alone was not seen, while low levels of ingestion of iC3b-E by patients' PMNs was noted. Monocytes from patients and controls expressed similar phagocytic activity in a fixed endpoint assay; however, the kinetics of phagocytosis by patients' monocytes was strikingly faster. Superoxide anion (O2.) and myeloperoxidase activities were similar to controls in PMN of four patients studied on day 1 of admission. PMN from two of three patients studied longitudinally showed an initial elevation in EIgG phagocytosis, which fell to normal levels by day 4, concomitantly with increased O2. generation and clinical improvement. Phagocytosis remained elevated in the third patient who did not clear his septicemia. Surface membrane FcRII, FcRIII, CR1, and CR3 were similar on patient and control PMN. In contrast, FcRI was increased on PMN of five of seven patients by monomeric IgG binding, and on two of two patients by monoclonal anti-FcRI binding. Thus, PMN and monocytes of patients with acute bacterial infections are either upregulated with regard to phagocytic function or are less susceptible to downregulation than are normal cells. This presumably would have a beneficial effect on host defenses during infection.

Adult↗