Modulation of Eicosanoid Production by Human Alveolar Macrophages Exposed to Silica in Vitro

Abstract

Repeated inhalationofsiLca dt can lead to hlammatlonam fibrosin hun iun and ineperimtal anial mods. The alveolar macrophage is believed to play a pivotal role in this process. Numerous macrophage-derived growth factors, cytokines, and arachidonic acid metabolites have been shown to contribute to inflammation and fibrosis. The objective of this study was to determine the eicosanoid production by human alveolar macrophages in response to silica exposure in vitro andtoassess the contribution ofalveolar macrophagestosilica-induced fibrosis and in tion. Macrophages were obtained from healthy volunteers and were incubated for 3 or 24 hr in the presence ofsilica (100, 60, andO Ag/mL).Supernatants were removed for eicosanoid analysis. Eicosanoids were analyzed by both high performance liquid chromatography and radiodmmunoassay. The data suggest that silica causes an increased release of leukotriene B4, leukotrienes C4/D4/E4, and 5-hydroxyeicosatetraenoic acid (5-HETE) after 3 hr and decreases in prostaglandin E2 and thromboxane B production after 24 hr of exposure to 100 Ag/mL silica. In addition, 12-HETE and 15-HETE production remained unchanged at eithertime point. These opposing effects seen with the metabolites of lipoxygenase and cyclooxygenase pathways could contribute to silica-induced fibrosis. The pattern ofekosanoid production after exposure to silica was different from that obtained when macrophages were stimulated with lipopolysaccharide for 3 or 24 hr, indicating that the response to the partides was not just due to general cellular activation.

Reaction of Human Alveolar Macrophages to Exposure toAspergillus fumigatusand Inert Particles

“…The silica particles did not influence the viability of cells, so there is probably not a toxic effect. In other studies silica particles have been shown to decrease secretion of two other substances, namely, thromboxane B 2 and prostaglandin E 2 (Brown et al, 1988;Koren et al, 1992). It should be of value to confirm these results with other insoluble particles.…”

Response of Alveolar Macrophages to Inhaled Particulates

“…While both mediators are known to have chemotactic activities, LTB 4 stimulates the secretory response of inflammatory cells, whereas PGE 2 is considered to have downregulatory effects on inflammatory cell function [44]. There are a number of studies indicating that LTB 4 produced by AM is closely associated with the inflammatory response caused by inhalation of various particulates.…”

“…There are a number of studies indicating that LTB 4 produced by AM is closely associated with the inflammatory response caused by inhalation of various particulates. Koren et al [44] demonstrated an increased LTB 4 release by AM upon in vitro exposure to silica, asbestos fibers, and carbonyl iron. Others reported that asbestos fibers induced an enhanced release of PGE 2 as well as an increased LTB 4 production by AM in vitro [45,46].…”

Agglomerates of ultrafine particles of elemental carbon and TiO2 induce generation of lipid mediators in alveolar macrophages.

“…Lipid mediators may play a major role in promoting or eliciting responses of lung tissue to air pollutants such as ozone (6,7), sulfurrelated species, especially sulfite (8,9), silica (10,11), and residual oil fly ash (12). Among the lipid mediators, platelet-activating factor and products of the 5-lipoxygenase (5-LO) pathway such as leukotriene B 4 (LTB 4 ) are known to stimulate immune cells such as polymorphonuclear neutrophil (PMNs) (13)(14)(15).…”