Prostaglandin E₂ inhibits and indomethacin and aspirin enhance, A23187‐stimulated leukotriene B₄ synthesis by rat peritoneal macrophages

Abstract

The calcium ionophore, A23187, stimulated leukotriene B4 (LTB4), thromboxane B2 (TxB2) and prostaglandin E2 (PGE2) synthesis by 4 day carrageenin‐elicited rat peritoneal macrophages. At concentrations of 2 × 10−7‐2 × 10−5 m indomethacin and aspirin enhanced A23187‐stimulated LTB4 synthesis and inhibited PGE2 and TXB2 formation. PGE2 inhibited A23187‐stimulated LTB4 and TXB2 formation as well as the augmentation of LTB4 release caused by aspirin and indomethacin. However, PGE2 was ineffective when the cells were challenged with arachidonic acid (AA). Dibutyryl adenosine 3′: 5′‐cyclic monophosphate (db‐cyclic AMP) partially inhibited A23187‐stimulated LTB4 production. Our results suggest that PGE2 inhibits macrophage LTB4 synthesis by limiting the availability of AA. Indomethacin and aspirin, possibly by removing the regulatory effect of PGE2, promote the synthesis of the pro‐inflammatory LTB4.

Leukotriene B4 stimulation of macrophage cyclooxygenase metabolite synthesis

“…Thus is could be that the basal release of AA is sufficient to maximally stimulate 6-keto PGFI~ formation. PGE 2 inhibits A23187-stimulated macrophage TXB2 formation and LTC4-stimulated macrophage PGE z synthesis is associated with a reduction in TXB 2 formation [1,2]. Thus, it could be that the apparent increase in LTB4-stimulated TXB 2 production observed during the 3 h incubation, compared to the 1 h data, was due to the relative reduction in PGE 2 synthesis.…”

“…LTC 4 also stimulates macrophage PGE 2 synthesis indicating that LTC4-stimulated fl-GLU secretion is self-limiting [1]. We have recently shown that calcium-ionophore (A23187)-stimulated macrophage LTB 4 synthesis is enhanced by indomethacin and inhibited by PGE 2 [2]. It is possible, therefore, that LTBa-stimulation of macrophage functions is also modified by an associated increase in endogenous PGE 2 formation.…”

Critical Role of Prostaglandin E2 Overproduction in Impaired Pulmonary Host Response following Bone Marrow Transplantation

“…PGE 2 has been shown to be a negative regulator of host defense (23)(24)(25)(27)(28)(29)(30)(31)(32)(33). To determine whether BMT mice were characterized by elevated levels of PGE 2 in vivo, we measured the amount of PGE 2 in the BALF and the lung homogenates of control and BMT mice.…”

Eicosanoid regulation of pulmonary innate immunity post-hematopoietic stem cell transplantation

“…Although phagocytes are capable of producing a variety of PG byproducts, we will focus on the regulatory functions of PGE 2 . PGE 2 is able to inhibit the following: leukocyte chemotaxis [2], AM phagocytosis and killing [3,4], PMN host defense functions [45], reactive oxygen intermediate production [67], AA release [34], LT synthesis [17], and the generation of multiple proinflammatory cytokines [13,46,53]. PGE 2 also enhances the production of the immunosuppressive cytokine IL-10 [43].…”