scholarly journals Augmentation of macrophage complement receptor function in vitro. I. Characterization of the cellular interactions required for the generation of a T-lymphocyte product that enhances macrophage complement receptor function.

1979 ◽  
Vol 150 (3) ◽  
pp. 653-675 ◽  
Author(s):  
J A Griffin ◽  
F M Griffin
Keyword(s):  
T Lymphocytes ◽  
Complex Disease ◽  
Peritoneal Macrophages ◽  
Fc Receptor ◽  
Microbial Pathogens ◽  
Complement Receptor ◽  
Complement Receptors ◽  
Cellular Interactions ◽  
Receptor Function

The function of complement receptors of mouse peritoneal macrophages was converted in vitro from mediating only attachment of macrophage complement receptor function was achieved by treating freshly explanted macrophages with supernates from cultures containing T lymphocytes and appropriately triggered macrophages. Fc receptor-mediated phagocyctosis by macrophages was required for the production of active supernates, for neither ingestion via the cells' complement receptors nor ingestion via nonimmunologic means was a sufficient stimulus for the macrophages' participation in the generation of supernatant activity. Fc receptor-triggered macrophages interacted by a contact dependent, but histocompatibility independent, mechanism with T lymphocytes, thereby signalling the lymphocytes to elaborate the active product. The possible significance of enhanced macrophage complement receptor function in inflammation, host defense against microbial pathogens, immune complex disease, and neoplasia is discussed.

scholarly journals Augmentation of macrophage complement receptor function in vitro. III. C3b receptors that promote phagocytosis migrate within the plane of the macrophage plasma membrane.

1981 ◽  
Vol 154 (2) ◽  
pp. 291-305 ◽  
Author(s):  
F M Griffin ◽  
P J Mullinax
Keyword(s):  
Plasma Membrane ◽  
Peritoneal Macrophages ◽  
Complement Receptor ◽  
Complement Receptors ◽  
Receptor Function ◽  
Surface Binding ◽  
The Difference ◽  
Macrophage Populations ◽  
Mouse Peritoneal Macrophages

We have previously reported that treatment with a unique lymphokine enables resident mouse peritoneal macrophages to phagocytize via their complement receptors and we have presented evidence that the lymphokine act by enabling complement receptor engagement by C3b ligands to generate a phagocytic signal, thereby linking the cell surface binding event with the intracellular phagocytic machinery. In the present experiments, we used immobilized immune complexes to study the topography of C3b receptors of resident mouse peritoneal macrophages treated with the lymphokine. Our results indicate that lymphokine treatment enables the macrophages' C3b receptors to migrate within the plane of the cells' plasma membrane and that manipulations of macrophages that abrogate one response to the lymphokine, complement receptor mobility, also abrogate the other response, complement receptor-mediated phagocytosis. These findings strongly suggest that lateral mobility of a ligand-bound receptor within the macrophage plasma membrane is an essential component of the phagocytic signal. Moreover, our results indicate that the difference in complement receptor function among various populations of macrophages is not due to the expression of different types of complement receptors by the different macrophage populations but rather to a difference in the relationship of the C3b receptor with other plasma membrane or intracellular components.

scholarly journals In vivo activation of macrophage C3 receptors for phagocytosis.

1985 ◽  
Vol 162 (1) ◽  
pp. 352-357 ◽  
Author(s):  
F M Griffin ◽  
P J Mullinax
Keyword(s):  
T Lymphocytes ◽  
Immune Complexes ◽  
Fc Receptors ◽  
Peritoneal Macrophages ◽  
Fc Receptor ◽  
Athymic Mice ◽  
Receptor Function ◽  
C3 Receptors

We assessed the effects of exposure to immune complexes in vivo on macrophages' Fc receptor function and C3 receptor function. Peritoneal macrophages from mice injected intraperitoneally with immune complexes were markedly impaired in their ability to phagocytize via their Fc receptors but had acquired the ability to phagocytize via their C3 receptors. In vivo activation of macrophages' C3 receptors for phagocytosis required T lymphocytes, because macrophages from athymic mice could not be activated by injection of immune complexes. The requirement for both T lymphocytes and immune complexes for activation of macrophages' C3 receptors in vivo is identical to the requirements for activation of macrophages' C3 receptors in vitro, suggesting that the mechanisms we have identified for activation of these receptors in vitro are the same mechanisms by which the receptors are activated for phagocytosis in vivo. The susceptibility of macrophages' Fc receptors to blockade by immune complexes and the activation of their C3 receptors for phagocytosis in a milieu containing immune complexes suggest that it may be macrophages' C3 receptors, not their Fc receptors, that are primarily responsible for promoting phagocytosis of opsonized microorganisms in immune hosts.

scholarly journals Effects of soluble immune complexes on Fc receptor- and C3b receptor-mediated phagocytosis by macrophages.

1980 ◽  
Vol 152 (4) ◽  
pp. 905-919 ◽  
Author(s):  
F M Griffin
Keyword(s):  
Immune Complexes ◽  
Fc Receptors ◽  
Fc Receptor ◽  
Complement Receptor ◽  
Complement Receptors ◽  
Phagocytic Function ◽  
Receptor Function ◽  
Coated Particles ◽  
C3b Receptor ◽  
Soluble Immune Complexes

The effects of ingestion of soluble immune complexes upon macrophage phagocytic function was studied. Ingestion of immune complexes severely impaired the macrophage's ability to ingest IgG-coated particles but did not alter its ability to interact with particles by means other than its Fc receptors. Treatment of macrophages that had ingested immune complexes with supernates containing the previously described lymphokine that augments macrophage complement receptor function failed to enhance the cells' interaction with either IgG-coated erythrocytes or zymosan particles but markedly enhanced their ability to phagocytize via their complement receptors. The possible significance of these findings in immunologically mediated inflammation is discussed.

scholarly journals Studies of the macrophage complement receptor. Alteration of receptor function upon macrophage activation.

1975 ◽  
Vol 141 (6) ◽  
pp. 1278-1290 ◽  
Author(s):  
C Bianco ◽  
F M Griffin ◽  
S C Silverstein
Keyword(s):  
Macrophage Activation ◽  
Quantitative Difference ◽  
Qualitative Difference ◽  
Fc Receptors ◽  
Significant Degree ◽  
Peritoneal Macrophages ◽  
Fc Receptor ◽  
Complement Receptor ◽  
Complement Receptors ◽  
Activated Macrophages

We have examined the roles of Fc receptors and complement receptors in mediating the interaction of sensitized sheep erythrocytes (E) with activated and with nonactivated mouse peritoneal macrophages. Both activated and nonactivated macrophages ingest IgG-coated erythrocytes [E(IgG)]; activated cells intest 1.5-2 times as man E(IgG) as do nonactivated macrophages. Thus, there is a quantitative difference in Fc receptor-mediated ingestion between activated and nonactivated macrophages. There is, however, a qualitative difference in function of complement receptors of activated and nonactivated macrophages. Nonactivated macrophages avidly bind complement-coated E [E(IgM)Ia1, but do not ingest them to a significant degree. Activated macrophages, on the other hand, bind and ingest E(IgM)C. The possibility of Fc receptor participation in mediating ingestion of E(IgM)C by activated macrophages was eliminated by blocking Fc receptors with an antimacrophage IgG fraction. Activated macrophages treated with antimacrophage IgG did not ingest E(igG) but did ingest both E(IgM)C AND E(IgM)C. Nonactivated macrophages treated with antimacrophage IgG did not interact at all with E(IgG). These cells bound, but did not ingest, E(IgM)C and E(IgM)C. Complement receptor-mediated ingestion is a marker for macrophage activation and may be physiologically important in the elimination of complement-coated particles.

scholarly journals Effects of immobilized immune complexes on Fc- and complement-receptor function in resident and thioglycollate-elicited mouse peritoneal macrophages.

1979 ◽  
Vol 150 (3) ◽  
pp. 607-621 ◽  
Author(s):  
J Michl ◽  
M M Pieczonka ◽  
J C Unkeless ◽  
S C Silverstein
Keyword(s):  
Immune Complexes ◽  
Fc Receptors ◽  
Cell Types ◽  
Peritoneal Macrophages ◽  
Complement Receptor ◽  
Complement Receptors ◽  
Receptor Function ◽  
Rabbit Antibody ◽  
Coated Surfaces ◽  
Mouse Peritoneal Macrophages

We have examined the Fc- and complement-receptor function of resident and thioglycollate-elicited mouse peritoneal macrophages plated on surfaces coated with rabbit antibody-antigen complexes and with complement. We derive four major conclusions from these studies. (a) The trypsin-resistant Fc receptors of resident and thioglycollate-elicited macrophages are completely modulated when these cells are plated on rabbit antibody-antigen complexes. Residual Fc receptor activity is a result of the incomplete modulation of trypsin-sensitive IgG2a receptors. (b) The complement receptors of thioglycollate-elicited macrophages, but not of resident macrophages, are modulated when these cells are plated on complement-coated surfaces. The capacity of the two cell types to modulate their complement receptors is correlated with their ability to ingest complement-coated erythrocytes. (c) The complement and Fc receptors of both types of macrophages move independently of one another. (d) Complement masks the Fc segments of IgG in immune complexes thereby rendering them ineffective as ligands for macrophage Fc receptors.

scholarly journals Regulation of elastase and plasminogen activator secretion in resident and inflammatory macrophages by receptors for the Fc domain of immunoglobulin G.

1984 ◽  
Vol 159 (1) ◽  
pp. 152-166 ◽  
Author(s):  
R Takemura ◽  
Z Werb
Keyword(s):  
Plasminogen Activator ◽  
Control Level ◽  
Fc Receptors ◽  
Fc Receptor ◽  
Complement Receptor ◽  
Complement Receptors ◽  
Membrane Bound ◽  
Inflammatory Macrophages ◽  
Secretion Rates ◽  
Stimulation Of

We have determined that the interaction of IgG-coated erythrocytes (EIgG) and complement-coated erythrocytes (EIgMC) with macrophage Fc and complement receptors, respectively, modulates the secretion of the neutral proteinases, elastase, and plasminogen activator. EIgG binding and ingestion stimulated secretion of elastase and plasminogen activator less than or equal to 6-fold and 20-fold, respectively, over the 3 d following treatment. Stimulation was dependent on the IgG titer bound to each erythrocyte and was detectable at greater than 6.2 X 10(3) molecules IgG/ erythrocyte (total 0.99 nM IgG in the culture). Cytochalasin B did not inhibit stimulation, indicating that the ingestion of ligands was not necessary. Binding of EIgG to the three subclass-specific Fc receptors (IgG2a, IgG2b/IgG1, IgG3) was effective. Stimulation of elastase secretion required continued exposure of ligands to cells for up to 24 h, whereas production of plasminogen activator, which has plasma membrane-bound forms as well as secreted forms, was stimulated by exposure for 2 h. The stimulated production of elastase and plasminogen activator by triggering Fc receptors was seen only when the initial secretion rates were low. Periodate- or thioglycollate-elicited macrophages, which have high rates of proteinase secretion, were not stimulated further. EIgMC, which are bound but not ingested by resident macrophages, stimulated elastase secretion transiently, and the rate of secretion returned to the control level by 24 h. Therefore, the mode of stimulation of neutral proteinase secretion by complement receptor differed from that of Fc receptor; stimulation by complement receptor possibly involves a limited release of enzyme from intracellular stores, rather than stimulating accelerated synthesis of enzyme. Erythrocytes coated with both complement and IgG showed both the transient increase in elastase typical of complement-mediated secretion and the sustained increase typical of Fc receptor-mediated secretion. These results suggest that macrophage Fc and complement receptors regulate secretion of proteinases by receptor-specific mechanisms.

scholarly journals Bacille Calmette-Guérin infection in the mouse. Regulation of macrophage plasminogen activator by T lymphocytes and specific antigen.

1978 ◽  
Vol 147 (4) ◽  
pp. 1175-1188 ◽  
Author(s):  
S Gordon ◽  
Z A Cohn
Keyword(s):  
T Lymphocytes ◽  
Plasminogen Activator ◽  
Macrophage Activation ◽  
Specific Antigen ◽  
Peritoneal Macrophages ◽  
Bacille Calmette Guerin ◽  
Vitro Assay ◽  
Purified Protein Derivative ◽  
Peritoneal Cells

High levels of plasminogen activator (PA) were induced in mouse peritoneal macrophages by infection with BCG, 2-6 X 10(7) viable organisms intravenously, followed 3-4 wk later by intraperitoneal challenge with purified protein derivative (PPD) 2 days before harvest. Macrophages obtained from infected animal without boosting showed little fibrinolytic activity, but challenge of Bacille-Calmette-Guèrin (BCG)-primed peritoneal cells with PPD in culture also enhanced macrophage PA 4- to 10-fold. Stimulation of macrophage PA by PPD depended on specifically sensitized thymus-derived (T) lymphocytes because it was abolished by pretreatment of BCG-primed peritoneal cells with anti-thy 1.2 antiserum and complement. A direct assay was developed in which nylon wool separated sensitized lymphocytes and PPD induced PA in macrophages from uninfected animals under defined conditions on 125I-fibrin. Enhanced macrophage fibrinolysis was proportional to concentration of PPD and the number of sensitized lymphocytes transferred. An indirect two-stage assay was also used to show that BCG-sensitized peritoneal cells released a soluble inducer of macrophage PA into the culture medium, after challenge with PPD. Induction of macrophage PA by PPD challenge in vitro made it possible to study the generation and activity of sensitized peritoneal lymphocytes at different stages of infection. Our results show that nonadherent peritoneal cells of BCG-infected mice provide a rich source of specifically sensitized lymphocytes and that macrophage activation is limited by continued availability of antigen, as well as sensitized lymphocytes. Induction of macrophage PA provides a sensitive, versatile, and rapid in vitro assay to study the role of lymphocytes and specific antigen in macrophage activation by BCG.

scholarly journals Trypanosoma cruzi: modification of macrophage function during infection.

1977 ◽  
Vol 146 (1) ◽  
pp. 157-171 ◽  
Author(s):  
N Nogueira ◽  
S Gordon ◽  
Z Cohn
Keyword(s):  
Trypanosoma Cruzi ◽  
Plasminogen Activator ◽  
Macrophage Activation ◽  
Specific Antigen ◽  
Peritoneal Macrophages ◽  
Complement Receptor ◽  
Trypanocidal Activity ◽  
Immunological Specificity ◽  
Mycobacterial Antigens

Infection of mice with Trypanosoma cruzi and subsequent intraperitoneal challenge with heat-killed trypanosomes elicits peritoneal macrophages which display in vitro microbicidal activity against trypomastigotes of T. cruzi. These cells also display other activated properties including rapid spreading, intense membrane activity, secretion of high levels of plasminogen activator, and ingestion mediated by the C3 receptor. An intravenous infection with BCG, followed by an intraperitoneal challenge with mycobacterial antigens brings about macrophages with similar properties. These criteria of macrophage activation were compared in normal and BCG- or T. cruzi-immune mice, with or without an intraperitoneal challenge with specific or unrelated antigens. Trypanocidal activity is displayed by both BCG- and T. cruzi-immune macrophages after intraperitoneal challenge with either antigen. Resident-immune macrophages from both T. cruzi- and BCG-infected mice show a trypanostatic, rather than trypanocidal activity. Macrophages from noninfected mice, challenged with the same antigens, show neither trypanostatic nor trypanocidal activity. Increased secretion of plasminogen activator shows a definite immunological specificity. Challenge with the specific antigen induces the appearance of macrophages secreting high levels of plasminogen activator, while unrelated antigens induce much smaller levels. Noninfected mice challenged with the same antigens do not display any enchancement in secretion. In contrast, increased spreading and phagocytosis mediated by the complement receptor are also displayed by cells from noninfected mice challenged with any of the agents tested.

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