Leukotriene A4 hydrolase and leukotriene C4 synthase activities in human chondrocytes: Transcellular biosynthesis of leukotrienes during granulocyte-chondrocyte interaction

Abstract

Objective. To investigate the cooperation of chondrocytes and polymorphonuclear cells (PMN) in the biosynthesis of leukotrienes (LT).Methods. PMN, resting and interleukin-lastimulated cultured human chondrocytes, and mixtures of both cell types were incubated with A23187 and/or 14C-arachidonic acid (14C-AA). To explore the presence of LTC, synthase and LTA, hydrolase, the chondrocytes were incubated with authentic LTA,. Eicosanoids were analyzed using high performance liquid chromatography techniques.Results. Chondrocytes formed only prostaglandin E, and minor amounts of 15-HETE and 11-HETE, the production of all of which was inhibited by 1 pM indomethacin. Incubation of PMN and chondrocytes produced more LTC, from endogenous and exogenous AA, and more LTB, from endogenous AA, than incubation of PMN alone, which was consistent with the presence of LTC, synthase and LTA, hydrolase activities in chondrocytes. Chondrocytes also slightly increased the level of PMN production of all 5-lipoxygenase (5-LO)-derived products from endogenous AA.Conclusion. Human chondrocytes form eicosanoids from AA only by the cyclooxygenase pathway. Chondrocytes cooperate in the transcellular biosynthesis of LT since they possess LTA, hydrolase and LTC, synthase activities and increase metabolism by the 5-LO pathway in PMN.

In vivo dual inhibition of cyclooxygenase and lipoxygenase by ML-3000 reduces the progression of experimental osteoarthritis: Suppression of collagenase 1 and interleukin-1? synthesis

“…The possible production of LTB 4 by chondrocytes is now under extensive examination, although previous studies have failed to identify 5-LO in these cells (12). LTs have been demonstrated to be potent factors in stimulating the synthesis of cytokines such as interleukin-1 (IL-1), IL-6, and IL-8 by synovial tissue (11).…”

Eicosanoid Transcellular Biosynthesis: From Cell-Cell Interactions to in Vivo Tissue Responses

“…This suggested that there was an important role for cell adhesion for transcellular biosynthesis to be efficient. Keratinocytes (Iversen et al, 1994) and chondrocytes (Amat et al, 1998) hydrolase and LTC 4 synthase. Alveolar macrophages were found to avidly take up exogenous LTA 4 and generate predominantly LTB 4 (Grimminger et al, 1991).…”

Inhibition of antigen-induced arthritis in guinea pigs by a selective LTB4 receptor antagonist LY293111Na

“…51, 2002 Leukotriene B 4 and guinea pig arthritis 547 consistent with these reports, because LY293111Na significantly inhibited the increase of MPO activity, a marker for tissue neutrophil content [30 -32], in the knee joint tissue at 24 h. These findings suggest that blockade of LTB 4 activity by LY293111Na seemed to lead to the decrease of PMN infiltration, and consequently ameliorated the cartilage and bone destruction induced by PMN-derived proteinases in guinea pig AIA [23]. In accordance with the present findings, Jovanovic et al recently examined the effect of ML-3000, a dual inhibitor of cyclooxygenase and 5-lipoxygenase, in dog OA model and concluded that LTB 4 has an important role in cartilage destruction [34], and another study revealed that chondrocytes cooperate with PMNs in the transcellular biosynthesis of LTB 4 [35].…”