Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Complement C5”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 973 records · Page 54Linked to original sources
PubMedDate not supplied

[Current aspects of chemotaxis of phagocytic cells].

Phagocytic cells, the first host defence against microbial attack, are remarkably mobile; they can move very rapidly to the infectious or inflammatory site. They migrate toward a chemotactic factor: C5a, lymphokines, bacterial products, leukotriene B4, etc. The binding of the chemotactic factor to its specific receptor on the cell leads to an activation of the phagocytic cell: the electric potential of the membrane changes, ionic fluxes and free calcium rate increase, arachidonic acid metabolites are produced, cyclic nucleotides are activated. This produces a change in shape, a polarization of the cell and, after cytoskeleton reorganization, migration of the cell towards the chemotactic factor. A constitutional or acquired abnormality of one of these steps induces a defect of chemotaxis for the phagocytic cells and severe infections.

Bacterial Proteins↗
PubMed1983

Role of toxic oxygen products from phagocytic cells in tissue injury.

The generation of toxic oxygen products from activated phagocytic cells represents an important pathogenic mechanism in tissue damage associated with inflammatory reactions that are characterized by the involvement of neutrophils or other phagocytic cells. The production of these toxic products from activated phagocytic cells is related to receptor activation on the surface of the cells. Most emphasis has been placed on studies in the lung where the production of these toxic metabolites by phagocytic cells, either in the vasculature or in the airway compartment of the lungs, has been demonstrated to result in endothelial cell injury or damage and destruction of alveolar lining cells. In some cases these reactions are progressive, resulting in parenchymal collapse and fibrosis. Naturally occurring protective factors have been demonstrated both within cells and in the plasma and interstitial fluid compartments. Although there is increasing evidence that in the shock syndrome complement activation products and toxic oxygen metabolites from activated leukocytes play important roles, the most direct evidence for related mechanisms comes in detailed studies of immune complex induced injury where a role for both O-2 and H2O2 has been clearly demonstrated. These facts indicate that toxic oxygen metabolites from activated phagocytic cells play important roles in a variety of pathological situations, and have provided new insights into intervention therapy.

Animals↗
PubMed1983

Anaphylatoxins inhibit C2 production.

Anaphylatoxins C5a and C3a and their des Arg derivatives inhibited C2 production by mononuclear phagocytes. C5a and C5adesArg which were approximately equipotent (IC50 = 10(-10) mol/l) were more effective than C3a (IC50 = 5 X 10(-8) mol/l) which was approximately 10-20-fold more potent than C3adesArg IC50 = 5 X 10(-6) mol/l). Inhibition of C2 production was only reversed slightly by the addition of either indomethacin or ETYA to the cultures. Intracellular levels of cAMP, were increased by anaphylatoxins. The level of cAMP showed a good inverse correlation with C2 levels in the culture supernatants. The data suggest that the reduction in C2 production produced by anaphylatoxins may be mediated by an increase in intracellular cAMP.

Anaphylatoxins↗
PubMed1984

Selective inhibition by phenytoin of chemotactic factor - stimulated neutrophil functions.

We have found that pretreatment of human neutrophils with phenytoin (0.05 to 0.8 mM) results in concentration-dependent, reversible inhibition of both superoxide anion generation and release of lysosomal enzymes (myeloperoxidase, lysozyme, beta-glucuronidase) provoked by either the synthetic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP) or the complement fragment C5a. In contrast, phenytoin did not inhibit either enzyme release or superoxide anion generation by neutrophils stimulated with phorbol myristate acetate or serum-opsonized zymosan particles. Phenytoin did not provoke leakage from neutrophils of the cytoplasmic enzyme, lactate dehydrogenase, and did not inhibit directed migration (chemotaxis) of neutrophils toward either FMLP or C5a. Specific binding of 3H-FMLP to neutrophil membrane receptors was not altered significantly by pretreatment of the cells with a wide range of concentrations of phenytoin. With flow microfluorometry and the fluorochrome, 3,3'-dipentyloxacarbocyanine, phenytoin was shown to prevent FMLP-induced changes in fluorescence intensity (i.e., apparent neutrophil membrane depolarization). These data indicate that various neutrophil functions may be regulated independently at other than the receptor level and that neutrophil chemotactic responses to FMLP and C5a do not appear to be dependent on membrane events registered by 3,3'-dipentyloxacarbocyanine.

Animals↗
PubMed1984

The in vivo effect of leukotriene B4 on polymorphonuclear leukocytes and the microcirculation. Comparison with activated complement (C5a des Arg) and enhancement by prostaglandin E2.

The effect of synthetic leukotriene B4 (LTB4) on chemotaxis in vivo (51Cr-polymorphonuclear leukocyte [PMN] accumulation) was examined and its potency compared with that of C5a des Arg-containing zymosan-activated plasma (ZAP). On a molar basis the amount of C5a des Arg calculated to be in our preparation of ZAP was found to be up to approximately 80 times more potent than LTB4, although in vitro the two chemotaxins have been reported to be about equipotent. ZAP is more representative of what may happen in vivo than its principal constituent C5a des Arg, but for a more precise comparison the purified and isolated peptide will have to be compared with synthetic LTB4. Whereas ZAP induced severe PMN-dependent microvascular injury (increase in vessel permeability [125I-albumin] and hemorrhage [59Fe-erythrocytes]), LTB4 only induced an increase in vascular permeability, and this occurred only in the presence of simultaneously injected prostaglandin E2 (PGE2). PGE2 also enhanced substantially the number of PMNs and the amount of exuded plasma at injection sites of the chemotaxins. However, unlike in two other reports, LTB4 did not cause an immediate transient increase in vessel permeability, nor did it enhance the permeability-increasing effect of bradykinin. Furthermore, unlike PGE2 LTB4 did not induce an increase in blood flow, but a decrease (57Co-microspheres). It is concluded that LTB4 may act as a host-derived chemoattractant in vivo, but, compared with that of ZAP (primarily activated complement), its role in acute inflammation is probably less significant than that of the complement-derived chemotaxin(s).

Animals↗
PubMed1984

Monokine generation as a consequence of binding of human C5a anaphylatoxin to specific cell-surface receptors.

The addition of human C5a to antigen-stimulated cultures results in dose-dependent augmentation of the primary antibody response to antigen. The specificity of this effect is confirmed by the ability of C5ades Arg, but not of the structurally analogous C3a anaphylatoxin, to act in a parallel fashion. This effect appears to be mediated by interaction of C5a with cells of the monocytoid/macrophage lineage. These cells have been shown to bear surface receptors specific for C5a. In order to examine the role of soluble mediators in these events, culture supernatants were generated from splenic adherent cells or macrophage cell lines after exposure to a brief pulse of human C5a. Supernatants from the macrophage-like cell line P388D1, which bears surface receptors for C5a, enhance the PFC response to antigen, whereas those from the closely related cell line P388, which lacks surface receptors for C5a, fail to cause enhancement. Supernatants from splenic adherent cells, which also bear C5a receptors, similarly augment the SRBC response. Active supernatants, but not those devoid of activity, contain IL-1 activity. None of the supernatants contain IL-2 activity. These observations suggest that the recently described role of human C5a as an immunopotentiating modulator is mediated by its ability to induce production of IL-1 upon binding to specific receptors at the macrophage cell surface.

Antibody Formation↗
PubMed1984

Characterization of the anaphylatoxin inactivator and chemotactic factor inactivator activities during cardiopulmonary bypass.

Complement activation productive of phlogistic products has been suggested as one of the major mechanisms of the pump lung syndrome associated with cardiopulmonary bypass (CPB) surgery. Recent studies have demonstrated the presence of circulating C3a antigens in the serum of patients undergoing CPB and have suggested that the vasoactive nature of C3a may contribute directly to the interstitial edema and vascular changes seen in pump lung syndrome. In an effort to unravel the underlying mechanisms of pump lung syndrome, we undertook investigations to determine whether CPB and associated complement activation would alter the serum levels of the major regulators of both C3a and C5a complement split products. These serum regulators designated chemotactic factor inactivator (CFI) and anaphylatoxin inactivator (AI) were measured in the serum of patients undergoing CPB. In these studies, we demonstrated that during CPB a rapid and dramatic drop in the anaphylatoxin inactivator activities occurred within the first 10 minutes of CPB. These lowered AI levels were maintained throughout the CPB but AI levels returned to normal within 24 hours postsurgery. CFI levels were generally maintained throughout the CPB surgery with only minimal depressions in CFI levels during or after CPB surgery. These studies clearly demonstrate that the major regulator system of the complement-derived vasopermeability factors (C3a and C5a) is dramatically depressed during cardiopulmonary bypass and may suggest that the mechanisms of interstitial edema associated with pump lung syndrome may at least, in part, be related to the loss of the serum regulator enzyme carboxypeptidase N, also designated AI.

Anaphylatoxins↗
PubMed1983

Complement-mediated leucoembolization: a mechanism of tissue damage during extracorporeal perfusions, myocardial infarction and in shock--a review.

The complement (C) system evolved as a beneficial antimicrobial system. However, when activated during extracorporeal perfusion as with haemodialysis or cardiopulmonary bypass modest pulmonary dysfunction associated with granulocyte aggregation and embolization can occur. When C activation is massive and prolonged, as with severe sepsis, trauma, or acute pancreatitis, severe pulmonary damage which is recognized as shock lung, or adult respiratory distress syndrome, may occur. Since ulcerating atherosclerotic plaques can also activate C, a mechanism by which myocardial infarcts may extend during the first few hours after infarction is also implied. Therapeutic ramifications of these conclusions are evident. Thus, high doses of corticosteroids or of nonsteroidal anti-inflammatory agents such as ibuprofen share the ability to prevent aggregation and embolization of stimulated granulocytes to patent vessels downstream and also inhibit their production of toxic oxygen radicals. These properties suggest the use of these agents in myocardial infarction and shock states, particularly shock lung, and appropriate clinical trials are awaited with interest.

Adrenal Cortex Hormones↗
PubMed1983

[Complement, granulocytes and pulmonary capillaries].

The activation, aggregation and adhesion of polymorphonuclear leukocytes on the endothelial wall of the pulmonary capillaries are responsible for lesions of variable severity on the alveolar-capillary membrane. The mechanism and the contribution of this leukocyte aggregation was studied to explain the respiratory abnormalities observed during the course of haemodialysis, leukapharesis and the end of extra-corporeal circulation. The activation of complement, by the formation of C5a is probably the initiator of this phenomenon. Based on these experimental models, the varied steps in the intra-capillary aggregation of leukocytes is envisaged as an explanation for the lesions in the acute respiratory distress syndrome, alveolitis caused by immune complexes and pulmonary toxicity caused by oxygen. Corticosteroids may inhibit leukocyte aggregation under certain conditions. These studies allow for a more precise pathophysiological approach for the use of steroids in their disorders.

Adrenal Cortex Hormones↗
PubMed1984

Analysis of the binding of fluorescent C5a and C3a to human peripheral blood leukocytes.

Fluorescein-labeled human C5a and C3a were prepared and utilized to analyze the binding of C5a and C3a to human neutrophils and mononuclear cells. The fluorescein derivatives of C5a (Fl-C5a) and C3a (Fl-C3a) contained approximately one fluorescein molecule per molecule of protein. Fl-C5a retained biologic activity as determined by neutrophil O2- production, enzyme release, receptor binding, and reaction with rabbit anti-C5a antibody. Fl-C3a was biologically active as measured by contraction of guinea pig ileal strips, and maintained 87% of its antigenic character when reacted with rabbit anti-human C3a. The binding of Fl-C5a and Fl-C3a to human neutrophils and mononuclear cells was assessed with the use of flow cytometry. Fl-C5a bound to greater than 90% of neutrophils, with an average ED50 ranging from 2.8 to 6.8 nM, depending on the method of analysis. Fl-C5a binding to neutrophils was specific and was not inhibited by the presence of formyl-methionyl-leucyl-phenylalanine (f-MLP), C3a, or casein. Fl-C5a binding was totally blocked by an excess of C5a. C5a des arg partially inhibited the binding of Fl-C5a to neutrophils, but was 1000-fold less effective than C5a. Similar experiments with mononuclear cells showed that Fl-C5a was bound by monocytes but not by lymphocytes. Fl-C5a binding to monocytes was blocked totally by C5a but not by C3a or f-MLP. Comparative binding studies with neutrophils, monocytes, and lymphocytes showed that Fl-C5a was bound by an average of 93% +/- 4 of neutrophils, 68% +/- 9 of monocytes, and 6% +/- 3 of lymphocytes. Fl-C3a did not show significant binding to neutrophils, monocytes, or lymphocytes. These studies demonstrate that fluorescein derivatives of C5a and C3a can be prepared with retention of biologic activity, and provide a means to evaluate the binding of C5a to individual cells.

Adult↗
PubMed1984

Pathophysiologic mechanisms of allergic and pseudo-allergic reactions to foods, food additives and drugs.

Allergic or pseudo-allergic reactions elicited by per os intake of foods, food additives or drugs may be based on one or several of the following immunopathologic mechanisms: 1) specific IgE bound to mast cells and/or basophils; 2) antigen-IgE soluble complexes hitting various target cells; 3) antigen-IgG complexes generating anaphylatoxins; 4) generation of anaphylatoxins by alternate pathway complement activation; 5) release of mast cell mediators by other direct triggering mechanisms (e.g., basic peptides, peptones); 6) effects on other target cells such as neutrophils and platelets; 7) reactions mediated by specific effector lymphocytes. While allergic reactions in a classical sense involve a sensitization process leading to the formation of specific immunologic agents such as antibodies or specific T lymphocytes, pseudo-allergic reactions appear to involve the same inflammatory mediators which are formed and/or released through different mechanisms and without the necessity for specific sensitization. The complexity of the phenomena possibly involved continues to create great difficulties in the objective diagnosis of food allergy.

Anaphylatoxins↗
PubMed1984

Effect of dialyzer reuse on complement activation and neutropenia in hemodialysis.

A prospective study of 10 patients undergoing hemodialysis showed that less neutropenia and complement activation occurred with dialyzer reuse. Neutrophil counts fell 95% +/- 5% (SEM) with first use and 66% +/- 8% and 48% +/- 10% with second and third uses, respectively (p less than 0.05). The production of complement component C5a-desarg, as measured by the bioassay granulocyte aggregation, was decreased by 96% +/- 1% and 93% +/- 2% with second and third uses, respectively (p less than 0.05). We investigated the role of the dialyzer disinfectant formaldehyde in decreased neutropenia. In vitro, formaldehyde inhibited granulocyte aggregation and chemotaxis and the dialyzer membrane's ability to generate granulocyte aggregating activity; however, this occurred only at concentrations higher than those likely to obtain in patients. The ability of dialysis membranes to generate granulocyte aggregating activity in plasma was decreased 55% +/- 5% by their prior sequential preincubation in plasma and then formalin (p less than 0.05) and extensive rinsing, which is similar to the circumstances obtaining with dialyzer reuse. Preincubation of membranes in plasma or formalin alone resulted in no change in the membrane's ability to generate granulocyte aggregating activity. We conclude that the exposure of membranes to both plasma and formalin during dialysis and storage is responsible for the decreased C5a-desarg production with reuse, probably because plasma proteins are fixed to the membrane in such a way that interrupts free interaction between the membrane and plasma complement components.

Agranulocytosis↗
PubMed1984

Resolution of pulmonary inflammation.

Mononuclear phagocytes are suggested to play a major orchestrating role in the resolution of inflammatory processes in the lung. Particular emphasis is placed on their participation in the progression from a lesion with neutrophils as the dominant infiltrating cell to one that contains macrophages, on the macrophage's role in removing neutrophils and cell debris, and on their promotion of repair mechanisms. It is suggested that monocytes must mature into macrophages before they are capable of active participation in the resolution of inflammation.

Animals↗