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Biomedical subjects

M Heideman

Publications and source records attributed to M Heideman.

At least 19 recordsLinked to original sources
PubMed1991

Activation of the complement cascade by trypsin.

In twenty-three patients with acute pancreatitis, the plasma levels of immunoreactive trypsin were determined with a RIA method. The patients were divided into groups according to the severity of the disease. Ranson's criteria and the development of multisystem organ failure were used for the classification. Elevated plasma levels of immunoreactive trypsin were found in all groups after admittance. Incubation of fresh human serum and plasma with bovine trypsin in concentrations between 10(-6) and 10(-4) M at 20 degrees C activated the complement cascade. The anaphylatoxins C3a and C5a were determined with a RIA and the terminal complement complex (TCC) with an ELISA method. C3a and C5a were released and TCC was formed. The effect of trypsin on leukocyte activation was determined with a chemiluminescence technique. Trypsin dissolved in saline did not activate the leukocytes. However, serum digested by trypsin-activated leukocytes in a dose-dependent manner. The present study supports the theory that trypsin can activate complement components and results in formation of split products which have potent vascular, and leukocyte activating effects.

Acute Disease↗
PubMed1990

Trypsin-induced vascular permeability and leukocyte accumulation in hamster cheek pouch: the role of complement activation.

Trypsin-induced acute inflammation was studied in hamster cheek pouch using intravital microscopy, correlative histology, and electron microscopy. Vascular permeability changes were monitored with intravital fluoroscopy, after intravenous injection of FITC-dextran (Mw 150,000), by counting the number of FITC-dextran leakages around the vessels. The number of extravasated polymorphonuclear leukocytes (PMNLs) was calculated by a histological technique. A dose-dependent increase in the number of FITC-dextran leakages, as well as the number of accumulated PMNLs, was found when trypsin was locally deposited in concentrations of 0.25-2.5 microM (15 microliters during 5 min). Local deposition of autologous serum treated with trypsin at final concentrations of 0.25-2.5 microM caused an increase in vascular permeability as equally pronounced as that of pure trypsin, but only a moderate PMNL accumulation which was not dose dependent. Trypsin at a 25 microM concentration resulted in numerous microbleedings and cessation of flow. The electron microscopy demonstrated inflammatory events (PMNL adhesion, diapedesis, and interstitial infiltration) in all treatment groups but they were more pronounced after trypsin exposure. Trypsin did not cause disintegration, cellular lysis, or increased mast cell degranulation. The permeability changes induced by trypsin (2.5 microM) and trypsinated serum (2.5 microM) were significantly suppressed by the addition of the chelating agent potassium-EDTA to the reaction mixture, indicating a calcium- or magnesium-dependent mechanism. Pretreatment of the animals with cobra venom factor (CVF), by which the plasma C3 concentration was reduced to less than 10%, inhibited the vascular leakages almost completely. The trypsin-induced accumulation of PMNLs was significantly reduced by potassium-EDTA as well as by pretreatment with CVF (P less than 0.01). These findings indicate a central role of complement activation in trypsin-induced acute inflammation in the hamster cheek pouch.

Animals↗
PubMed1990

Complement activation and reinfusion of wound drainage blood.

Eighteen patients undergoing total hip replacement (n = 13) or knee arthroplasty (n = 5) due to osteoarthritis or osteoarthrosis were prospectively studied in an investigation of complement activation and anaphylatoxin release in association with reinfusion of aspirated wound blood. Twelve of the patients needed blood transfusions and received an average of 390 +/- 75 ml (+/- SD) of autologous blood within 45 min. Plasma complement components, anaphylatoxins, and inhibitors were studied 1 min before and 15 min after the start of and 15 min after the completion of autologous transfusion. Samples also were taken from the collected blood, before and after passing it through a microporous filter. Blood gases and systemic complement samples were drawn simultaneously. There were no significant changes in systemic complement variables before, during, or after transfusion of autologous blood. However, in the aspirated blood, increased concentration of anaphylatoxins (C3a and C5a) and terminal complement complexes (TCC) were present (P less than 0.001). There were no differences observed between samples drawn before and after filtration of the blood. The concentration of C5 was less in the collected blood than in the systemic blood (P less than 0.05). No changes in blood gases were observed. This study demonstrated that postoperatively salvaged whole blood underwent anaphylatoxin formation and complement activation. However, after reinfusion of this blood, neither systemic complement activation nor clinical complications were observed.

Adult↗
PubMed1990

Accumulation of anaphylatoxins and terminal complement complexes in inflammatory fluids.

The presence of anaphylatoxins (C3a and C5a) and terminal complement complexes (TCC) in different inflammatory fluids and plasma was studied in 33 patients. Anaphylatoxins were assayed using a radioimmunoassay technique, and the terminal complement complexes were determined by an ELISA method. Patients with peritoneal (n = 14), pleural (n = 7), pericardial (n = 6) or burn bullae fluid (n = 6) were studied. High C3a and TCC concentrations were found in all these fluids. Elevated C3a and TCC concentrations in inflammatory fluids were found not only in patients with elevated plasma C3a and TCC concentrations, but also in patients with normal plasma levels. No increases in C5a concentration were observed in pleural or burn bullae fluid. In one patient with pericarditis, and in subjects with acute pancreatitis with ascites, high C5a levels were found in the fluid. However, the high TCC concentration in the fluids suggests that C5a had been formed but was probably removed by leucocytes present in the fluid.

Acute Disease↗
PubMed1989

Anaphylatoxin generation in acute pancreatitis.

Fifty-one patients with elevated serum amylase and clinical signs of acute pancreatitis were studied prospectively. The concentrations of anaphylatoxins (C3a and C5a) were measured with a radioimmunoassay and the activity of their inactivator was determined. The pancreatitis was classified as mild, moderate, or severe according to Ranson's 11 signs, appearance of peritoneal fluid, and development of multisystem organ failure (MSOF). Plasma C3a and C5a concentrations were elevated during attacks of acute pancreatitis. Anaphylatoxin levels correlated with the severity of the disease (C3a, P less than 0.001; C5a, P less than 0.05). The highest and most persistent levels were found in the group with MSOF. C3a levels decreased rapidly during recovery. In patients with complications like abscess or pseudocyst, the C3a elevation persisted until adequate treatment was instituted. In this study, no significant changes of the inactivator levels were found, except at discharge when the inactivator level of the severe group was elevated compared to that of the moderate and mild groups (P less than 0.05).

Acute Disease↗
PubMed1989

Altered concentrations of terminal complement complexes, anaphylatoxins, and leukotrienes in the coronary sinus during cardiopulmonary bypass.

The aim of this study was to determine if the hypoperfused heart activates complement with formation of anaphylatoxins, terminal complement complexes (TCC), or leukotrienes during cardiopulmonary bypass. Fifteen patients undergoing elective cardiopulmonary bypass surgery were studied regarding complement and leukotriene activation. Blood samples were drawn serially from the radial artery and coronary sinus. The plasma concentrations of the complement components C1INH, C3, C4, and C5 decreased during the procedure, whereas C3a and TCC increased. Protamine reversal of heparin further increased the plasma levels of C3a and TCC. No significant changes in plasma levels of C5a and leukotriene C4 were observed during cardiopulmonary bypass. The activity of the anaphylatoxin inactivator (AI) decreased in both the radial artery and the coronary sinus. There were no significant differences between the concentrations of complement components and leukotriene C4 in blood from the radial artery and coronary sinus. The levels of C3a and TCC increased and C1INH, C3, C4, C5, and the anaphylatoxin inactivator activity decreased to the same extent in the coronary sinus and the radial artery. Thus, the heart does not appear to be the primary site for the altered concentrations of these endogenous vasoactive substances.

Aged↗
PubMed1989

Complement activation and anaphylatoxin (C3a and C5a) formation in preeclampsia and by amniotic fluid.

The aim of this study was to determine whether the biologically active complement peptides C3a and C5a are formed in pregnancy and whether amniotic fluid can activate complement. C3a and C5a are formed when complement is activated. They increase smooth-muscle contraction, vascular permeability, and histamine release from mast cells and basophils. Thirty pregnant women were studied, 16 with uncomplicated and 14 with preeclamptic pregnancies. The plasma C3a and C5a concentrations before delivery were significantly higher in the preeclamptic than in the normal group. The concentrations returned to normal within 1 week. Plasma, serum, and amniotic fluid from 12 pregnant women (eight uncomplicated and four preeclamptic pregnancies) were drawn in connection with delivery. Amniotic fluid was incubated in fresh autologous serum at 37C for 15 minutes. A dose-dependent formation of C3a and C5a was registered with increasing amounts of amniotic fluid.

Adult↗
PubMed1988

Terminal complement complexes and anaphylatoxins in septic and ischemic patients.

Terminal complement complex (TCC) and anaphylatoxin formation in 18 patients with sepsis and 20 patients with acute limb ischemia were studied before the start of treatment and seven days later. The septic or ischemic patients had elevated levels of plasma TCC before start of therapy. In successfully treated patients these concentrations were within the normal range one week later. Similarly, the plasma anaphylatoxin level was increased before therapy and returned to the normal range within seven days. Escherichia coli incubated in vitro in fresh human serum at body temperature started formation of TCC in a dose-related manner. As complement will induce cellular lysis via TCC and edema via anaphylatoxins, anemia and impaired respiration in these patients may be influenced by increased concentrations of terminal complement complexes and of C3a and C5a.

Aged↗
PubMed1988

Anaphylatoxin formation in sepsis.

Complement activation and anaphylatoxin formation were studied in 27 septic patients. The patients were treated with antibiotics and high-dose corticosteroids. Blood samples were drawn on admission and every week thereafter. Plasma levels of complement components C1INH, C3, C4, and C5 were low before the start of treatment but were above normal one week later in both successfully and unsuccessfully treated patients. In contrast, plasma levels of anaphylatoxins C3a/C3adesArg and C5a/C5adesArg were elevated on admission. After successful treatment, plasma levels of C3a/C3adesArg and C5a/C5adesArg returned to normal within one week. Nine patients had ongoing sepsis one week after the start of treatment and a persistent rise in anaphylatoxin concentration. They developed multisystem organ failure with respiratory, hepatic, and renal insufficiency. In vitro studies of Escherichia coli incubation in fresh serum indicated a dose-related formation of C3a/C3adesArg and C5a/C5adesArg. High concentrations of methylprednisolone inhibited the anaphylatoxin formation in vitro.

Adult↗
PubMed1988

Inhibition of complement activation by high-dose corticosteroids in total hip arthroplasty.

Anaphylatoxins are released during total hip arthroplasties (THA) when methylmethacrylate is used. These toxins may be responsible for hemodynamic and pulmonary instability during surgery. Recent studies have shown that the release of anaphylatoxins may be inhibited by high-dose corticosteroids (HDC). In a double-blind study 30 consecutive patients with osteoarthritis or failed hip fractures were randomized into two groups; 15 patients received HDC at the beginning of the operation and 15 patients, designated the control group, received infused saline. Anaphylatoxin formation, arterial oxygen tension, and blood pressure were determined preoperatively, during the operation, and one day postoperatively. The patients who received HDC had no significant alteration regarding the anaphylatoxins or arterial oxygen tension during surgery. However, in the control group elevated C3a levels and decreased PaO2 levels were found. Corticosteroids therefore inhibit complement activation and anaphylatoxin release in hip arthroplasty surgery.

Aged↗
PubMed1987

In vivo determination of modulated migration of radiolabeled leukocytes.

A method to determine migration of phagocytic cells in vivo has been evaluated. It was used to analyze leukocyte migration during ischemia, peritonitis, and after pretreatment with methylprednisolone. Phagocytic cells were labeled in vitro with 150 megabecquerel (4.05 mCi) of technetium Tc 99m colloid and reinfused. Saline 0.03 mg and 3.0 mg of endotoxin per kilogram per rat were injected subcutaneously in duplicate. Four hours later, a standardized amount of skin and subcutaneous tissue from the area of injection was removed and weighed. A dose-related accumulation of radiolabeled leukocytes to endotoxin was found in healthy controls but not in animals with hypoperfusion or peritonitis or those pretreated with methylprednisolone. This in vivo method to calculate leukocyte migration will give reproducible results with a mean difference between duplicate samples of less than 6%.

Animals↗
PubMed1987

The ischaemic leg as a source of complement activation.

Complement activation before and after surgical resection was studied in 40 patients with ischaemic legs (17 with acute and 23 with chronic ischaemia). Plasma anaphylatoxin concentrations (C3a and C5a) and anaphylatoxin inhibitor (AI) activity were studied pre-operatively, and 1 h, 24 h and 1 week postoperatively. Increased plasma anaphylatoxin concentrations were found pre-operatively. Anaphylatoxin levels in plasma had returned to normal one week postoperatively. Patients with acute ischaemia had higher plasma C3a and C5a pre-operatively and during the first 24 h postoperatively than patients with chronic ischaemia. Anaphylatoxins increase vascular permeability, smooth muscle contraction and histamine release from mast cells. Their enhanced activity might be one of the explanations for respiratory, hepatic and renal insufficiency before surgical resection in patients with extensive ischaemia.

Aged↗
PubMed1987

IgG binding to cytoskeletal intermediate filaments activates the complement cascade.

The cellular plasma membrane becomes permeable to macromolecules during the cell injury process. This results in exposure of the interior of the cell to plasma proteins and to high-affinity binding of the Fc part of IgG to intermediate filaments (Hansson, G K, Starkebaum, G A, Benditt, E P & Schwartz, S M, Proc natl acad sci USA 81 (1984) 3103). Such IgG binding could be an early step in a process that serves to eliminate the injured cell. We have now identified its effect on the complement system. Intermediate filaments were reconstituted in vitro from purified vimentin, and incubated with plasma proteins. Cross-linker experiments showed binding of the heavy chain of IgG to vimentin, indicating that the vimentin protein carries an Fc-binding site. In contrast, no direct binding of complement factor Clq to vimentin could be detected. Binding of both IgG and Clq could, however, be detected by immunofluorescence when cytoskeletons of cultured endothelial cells were incubated with fresh serum. Therefore, IgG binding to filaments in the presence of serum is accompanied by Clq binding to IgG. This was in turn followed by fixation of C4 and C3 to intermediate filaments in a process that was dependent on both Ca2+, Mg2+ and Clq, indicating that it was part of a complement activation via the classical pathway. Exposure of fresh serum to intermediate filaments also resulted in production of the anaphylatoxic complement cleavage fragment. C3a, with a dose-response relationship between the amount of filaments present and the amount of C3a generated. Chemotactic activity towards granulocytes and monocytes was also generated by exposure of serum to intermediate filaments, and this activity was dependent on the presence of complement factor C5 and on the classical complement activation cascade, implying that it was due to the C5a peptide. Exposure of the interior of the cell to plasma proteins thus results in binding of IgG to intermediate filaments and activation of the complement cascade via the classical pathway. This, in turn generates bioactive mediators which may recruit leukocytes to the injured cell (C5a) and have profound effects on vascular permeability (C3a, C5a). We propose that this is part of a scavenger mechanism for the elimination of damaged cells.

Binding Sites↗
PubMed1987

Anaphylatoxin formation in plasma and burn bullae fluid in the thermally injured patient.

Plasma anaphylatoxins (C3a and C5a) were measured in 19 thermally injured patients with a mean total burned surface area of 39 per cent (range 10-90 per cent) of partial and full skin thickness loss. Extensive burns were associated with increased anaphylatoxin activity. Patients with greater than 50 per cent burned surface area had higher plasma C3a and C5a concentrations than patients with 10-25 per cent burns (P less than 0.001) 1 week after injury. Six out of seven patients with greater than 50 per cent burned surface area developed adult respiratory distress syndrome (ARDS) and four out of seven bacteraemia. Twelve patients had 10-25 per cent burns and none of them developed ARDS or bacteraemia. The mean C3a concentration per millilitre of fluid from the burn bullae from nine different individuals was 2570 +/- 260 ng/ml. The C5a content in fluid from the bullae did not differ from the corresponding plasma range. Increased anaphylatoxin activity might explain extensive extravasation of fluid in burned patients. This increase might also be one reason for leukocyte accumulation in burned areas.

Adult↗
PubMed1987

Complement and anaphylatoxin responses to cross-clamping of the aorta. Studies during general anaesthesia with or without extradural blockade.

Complement activation and anaphylatoxin formation were studied in 28 patients undergoing aortic reconstructive surgery under general anaesthesia. In 12 of the patients an extradural catheter was placed in the L1-2 space and 2% mepivacaine was injected until blockade reached the T4 level. The remaining 16 patients were operated upon under general anaesthesia alone. Complement activation was not obvious until aortic cross-clamping. The release of anaphylatoxin was less pronounced during cross-clamping in the extradural group.

Aged↗