IgE-dependent release of leukotriene C4 from alveolar macrophages

Rankin, John A.; Hitchcock, Margaret; Merrill, William; Bach, Michael K.; Brashler, John R.; Askenase, Philip W.

doi:10.1038/297329a0

Cited by 174 publications

(42 citation statements)

References 35 publications

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“…It can also be argued that druginduced reductions of in vivo anaphylactic reactions in the present system might be due to reduced nonhistamine mediator production by cells other than mast cells. To give one example of such a possibility, leukotriene C4 was recently reported to be produced by rat alveolar macrophages in an IgE-dependent process (Rankin et al, 1982). However, histamine is a mediator of main importance in guinea-pigs (Andersson, 1982 (Andersson 1981).…”

Section: Discussionmentioning

confidence: 99%

Changes in bronchial anaphylactic reactivity induced in guinea‐pigs by long‐term treatment with histamine H₂‐agents

Andersson¹,

Bergstrand²

1984

British J Pharmacology

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Guinea‐pigs were sensitized to ovalbumin (OA) by immunization regimens chosen to cause antigen‐induced bronchial anaphylactic responses mediated mainly either by IgE‐like antibodies or by IgG1‐like antibodies. Treatment of the IgE‐producing animals for three weeks with the histamine H2‐receptor antagonist cimetidine (1 mg kg−1 i.p. once a day) or with the H2‐agonist dimaprit (0.1, 1.0, or 10 mg kg−1 i.p. once a day) led to a significantly reduced bronchial response capacity compared with that of the saline‐treated controls challenged intravenously with antigen one week after the end of treatment. The changes were biphasic and not strictly dose‐dependent. In contrast, acute treatment of immunized animals with a single dose of cimetidine (10 or 30 mg kg−1 i.v.) or dimaprit (1 or 10 mg kg−1 i.v.) 2 min before challenge with OA did not significantly affect the bronchial anaphylactic response. However, long‐term treatment with cimetidine (10 mg kg−1) or the dimaprit analogue, S‐[4‐(N, N‐dimethylamino)‐butyl] isothiourea (SKF Compound 91488) (1 mg kg−1), which is reported not to activate H2‐receptors, had no effect on the response capacity. Treatment with cimetidine (1 mg kg−1) or dimaprit (1 mg kg−1) did not influence the response capacity to antigen challenge in IgG1‐ type animals. Dimaprit (1 mg kg−1) did not affect the responsiveness to intravenous provocation with histamine in ‘IgE‐type’ animals. Antigen‐induced release of histamine from chopped lung tissue in vitro was not significantly affected in ‘IgE‐type’ animals treated with cimetidine (1 mg kg−1) or dimaprit (1 mg kg−1). Treatment of immunized animals with cimetidine or dimaprit one week before and one week after a booster injection of antigen also led to reduced response capacity compared with that of saline‐treated controls. However, the serum levels of IgE‐like homocytotropic antibodies of these animals were not reduced; on the contrary, those of IgG1‐antibody were increased in dimaprit‐treated animals. These data show that intermittent treatment with histamine H2‐agents reduces reagin‐mediated anaphylactic response capacity in vivo in actively sensitized guinea‐pigs by an as yet undefined mode of action.

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Section: Discussionmentioning

confidence: 99%

Changes in bronchial anaphylactic reactivity induced in guinea‐pigs by long‐term treatment with histamine H₂‐agents

Andersson¹,

Bergstrand²

1984

British J Pharmacology

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“…The in vivo stimulus for 5-LO activation in AM remains to be determined. However, one substance which is both sufficient to stimulate LT synthesis in AMs in vitro (31,32) and is present in the circulation of some patients with IPF (33) is immune complexes. Alternatively, it is possible that cytokines such as interleukin-8, also reported to be increased in the lower respiratory tract of patients with IPF (9, 10), could stimulate or prime AMs for enhanced LT synthesis (34).…”

Section: Discussionmentioning

confidence: 99%

Constitutive activation of 5-lipoxygenase in the lungs of patients with idiopathic pulmonary fibrosis.

Wilborn¹,

Bailie²,

Coffey³

et al. 1996

J. Clin. Invest.

172

140

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Idiopathic pulmonary fibrosis (IPF) is a progressive disorder characterized by inflammation, fibroblast proliferation, and accumulation of extracellular matrix proteins. Leukotrienes (LTs) are pro-inflammatory and pro-fibrogenic mediators derived from the 5-lipoxygenase (5-LO) pathway of arachidonic acid metabolism. They are thought to play a role in a number of disease processes, but have received relatively little attention in investigations into the pathogenesis of IPF. In this study, we measured the levels of immunoreactive LTs B 4 and C 4 in homogenates of lung tissue obtained from patients with newly diagnosed, untreated IPF, as compared to levels measured in homogenates of uninvolved nonfibrotic lung tissue from patients undergoing resectional surgery for bronchogenic carcinoma. Compared to homogenates of nonfibrotic control lung, homogenates from IPF patients contained 15-fold more LTB 4 and 5-fold more LTC 4 . IPF homogenate levels of LTB 4 were significantly correlated with histologic indices of both inflammation ( r ϭ 0.861) and fibrosis ( r ϭ 0.926). Activation of 5-LO is known from in vitro studies to be associated with localization of the enzyme at the nuclear membrane. Immunohistochemical staining for 5-LO protein in alveolar macrophages (AMs) demonstrated that such an "activated" localization pattern was significantly more frequent in IPF lung (19.2 Ϯ 3.3% of cells) than in control lung (9.3 Ϯ 0.9%); this localization pattern was rarely seen (3.2%) in sections from a truly normal transplant donor lung. Consistent with these data, AMs obtained from IPF patients by bronchoalveolar lavage, purified by adherence, and cultured in the absence of a stimulus for 16 h elaborated significantly greater amounts of LTB 4 and LTC 4 than did control AMs obtained from normal volunteers. These data indicate that the 5-LO pathway is constitutively activated in the lungs of patients with IPF, and the AM represents at least one cellular source of LT overproduction in this disorder. We speculate that LTs participate in the pathogenesis of IPF, and their overproduction in this disorder may be amenable to specific pharmacotherapy. (

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“…Metzger et al have shown that the total number of peroxidase-positive AM obtained from BAL fluid is increased at 48 and 96 h after allergen ehallenge, suggesting that a population of monocytes has entered the lung from the local vascular compartment (60). Rankin and colleagues showed that normal AM can be activated by monoclonal IgE and specific antigen to generate both LTC4 and LTB4 (68,69). …”

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confidence: 99%

The role of the macrophage in asthma

Lane

Lee

1994

Allergy

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Aeeumulating evidence implicates eells ofthe mononuclear phagocyte lineage in the pathogenesis of bronchial asthma. The evidence for involvement of peripheral blood monoeytes (PBM) and alveolar macrophages (AM) in the pathogenesis of asthma stems from functional studies on peripheral blood monocytes and analysis of the fluid and cellular phases of bronchoalveolar lavage (BAE) samples, and, more recently, from histologic material obtained from endobronchial biopsy in vivo. -• Peripheral blood monocytesIn 1975, Capron etal. produced evidence of IgE receptors on macrophages by showing the role of IgE antibodies in macrophage-dependent cytotoxic damage to parasites (12). This receptor is similar, if not identical, to the Fc,.r found on T and B cells and is referred to as FC.TJ, as it differs in both structure and function from the Fc,.r, found on mast cells and basophils (77). The most important functional difference is that the Fc,,r2 on macrophages is of a lower afiinity (i.e., an estimated dissociation constant for monomeric IgE binding to macrophages and U937 cells of 10|.iM) and is preferentially activated by immune complexes (40). Approximately 5-10% of PBM and AM bear Fc^r, (56,77). This percentage rises to 20% in mildly atopic asthmatic subjects and can be downregulated by eortieosteroid treatment (58).PBM from asthmatic subjeets have enhaneed complement receptor expression (CRE) in the presence or absence of casein, as compared with normal controls (42). Furthermore, the numbers of PBM that form rosettes with eomplenicnt-coated sheep erythroeytes are increased in asthmatic subjects after allergen bronchoprovocation, but not after histamine-induced bronchoconstriction (13). In asthmatic subjeets who respond to corticosteroids (corticosteroid-sensitive (CS) asthmatic subjects), these levels revert to normal after 7 days' treatment with prednisolone, whereas in patients who fail to improve clinically with corticosteroids (corticosteroid-resistant (CR) asthmatic subjects), these levels remain elevated (42). In addition, it has been shown that in vitro colony formation in soft agar by PHA-stimulated mononuelear cells is inhibited by methylprednisolone in CS subjects, but not in CR subjects. The origin of this in vitro resistance was found to be monocyte-derived, rather than lymphocyte-derived (67). We have shown that the expression of the activation antigens CR-1, CR-3, and class II molecules on cultured PBM is elevated in asthmatic subjects, as compared with normal eontrol subjects (89). Furthermore, this enhanced receptor expression is suppressed by hydroeortisone 201 Lane et al.in CS, but not in CR, asthmatic subjects, suggesting ongoing PBM activation in the presence of corticosteroids. Interactions between monocytes and granulocytesActivated PBM generate a number of proinflammatory molecules which can influence the activity of other cell types. For instance, supernatants from activated PBM modulate arachidonic acid metabolism by the cyclooxygenase and lipoxygenase pathway in maerophages, fibroblasts, and gr...

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IgE-dependent release of leukotriene C4 from alveolar macrophages

Cited by 174 publications

References 35 publications

Changes in bronchial anaphylactic reactivity induced in guinea‐pigs by long‐term treatment with histamine H₂‐agents

Changes in bronchial anaphylactic reactivity induced in guinea‐pigs by long‐term treatment with histamine H₂‐agents

Constitutive activation of 5-lipoxygenase in the lungs of patients with idiopathic pulmonary fibrosis.

The role of the macrophage in asthma

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IgE-dependent release of leukotriene C4 from alveolar macrophages

Cited by 174 publications

References 35 publications

Changes in bronchial anaphylactic reactivity induced in guinea‐pigs by long‐term treatment with histamine H2‐agents

Changes in bronchial anaphylactic reactivity induced in guinea‐pigs by long‐term treatment with histamine H2‐agents

Constitutive activation of 5-lipoxygenase in the lungs of patients with idiopathic pulmonary fibrosis.

The role of the macrophage in asthma

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Product

Resources

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Changes in bronchial anaphylactic reactivity induced in guinea‐pigs by long‐term treatment with histamine H₂‐agents

Changes in bronchial anaphylactic reactivity induced in guinea‐pigs by long‐term treatment with histamine H₂‐agents