IgE immune complexes stimulate arachidonic acid release by mouse peritoneal macrophages.

Abstract

Resident mouse peritoneal macrophages were labeled with [3H]arachidonic acid and challenged with Sephadex beads coated with immune complexes of IgE and antigen. Arachidonic acid release by the cells was assessed by the quantity of radiolabel recovered from the culture medium. Freshly isolated macrophages responded to IgE immune complexes with a release of [3H]arachidonic acid that was linear for 1-2 hr. The magnitude of the response was dependent on both the number of immune complex-coated beads and on the degree of opsonization of the beads. Under conditions of maximal stimulation, macrophages challenged with IgE immune complex-coated Sephadex released 23 + 4.5% of their incorporated radiolabel. This is compared to values of 34.2 ± 0.5% and 38.1 ± 3.3% for cultures that received IgG immune complex-coated Sephadex or zymosan, respectively. Macrophages did not release arachidonic acid upon exposure to soluble IgE and antigen given sequentially or simultaneously, and soluble IgE did not inhibit the cells' response to IgE immune complexes. Incubation of macrophages for longer than 3 hr prior to challenge resulted in a selective loss in the cells' ability to respond to IgE immune complexes. After 16 hr of culture, macrophages released only 3.9 ± 0.3% of their incorporated 3H on exposure to IgE immune complexes; however radiolabel release in response to zymosan (42.0 ± 0.8%) was identical to that of freshly isolated cells. These data indicate that macrophages are capable of releasing arachidonic acid in response to preformed particulate immune complexes ofIgE and antigen. Because Sephadex beads are too large to be interiorized by the cells, this response results from the interaction of the immune complexes with the macrophage plasma membrane.Resident mouse peritoneal and pulmonary macrophages secrete large quantities of arachidonic acid metabolites in response to unopsonized zymosan and particulate immune complexes of IgG and antigen (1-4). A major arachidonic acid metabolite of macrophages is the slow-reacting substance, leukotriene C (5S, 6R)-5-hydroxy-6-S-glutathionyl-7, 9-trans-11, 14-cis-icosatetraenoic acid) (4-6). Traditionally, the production of slow-reacting substance of anaphylaxis has been associated with IgE-mediated, immediate hypersensitivity reactions (7) in which macrophages have no known role. Recently, however, studies have indicated that macrophages bear a receptor for the Fc-fragment of IgE, suggesting that these cells may respond to IgE-related stimuli (8)(9)(10). In this paper, we report that resident mouse peritoneal macrophages prelabeled with [3H]arachidonic acid release 20-30% of their incorporated radiolabel in response to a challenge with particle-bound immune complexes of IgE and antigen. Previous work has shown that arachidonic acid released by resident peritoneal macrophages is quantitatively metabolized by the cyclooxygenase and lipoxygenase pathways (1, 4, 5). These results suggest that, through the synthesis of arachidonic acid metabolites, the macrophage may be a-primary re...

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