Biosynthesis of sulfidopeptide leukotrienes via the transfer of leukotriene A4 from polymorphonuclear cells to bovine retinal pericytes.
Administration of exogenous sulfidopeptide leukotrienes (LTs) is associated with enhanced microvascular permeability. In addition, endogenous LTs have been implicated as participants in permeability (nonhydrostatic) edema formation. The source of LTs for interaction with the microvasculature is, however, unknown. We hypothesized that pericytes contribute to vascular LT synthesis. Under basal conditions and after incubation with either the calcium ionophore, A23187 (0-1 microM), or arachidonic acid (20 microM), bovine retinal pericytes (BRPs) did not produce significant amounts of sulfidopeptide LTs. In contrast, in the presence of polymorphonuclear leukocytes (PMNs), which can synthesize LTA4, but not sulfidopeptide leukotrienes, incubation of BRPs with A23187 resulted in dose-dependent increases in LTC4/D4/E4 production (peak: 35.4 +/- 5 pg/microg protein; n = 12). Similarly, BRPs, incubated with exogenous, authentic LTA4 (10 microM), synthesized sulfidopeptide LTs (peak: 18.9 +/- 5 pg/microg protein, n = 3). Preincubation (30 min) of BRPs with PMNs and the lipoxygenase inhibitor, esculetin (1 x 10(-)4 M; n = 12), reduced peak A23187-induced production of LTs by 63.9 +/- 7%. Finally, Northern blot analysis revealed mRNA for 5-lipoxygenase to be present in human and bovine PMNs, but not in BRPs. These results suggest that pericytes produce sulfidopeptide LTs only when provided with LTA4 from an external source such as the PMN. Interactions between pericytes and PMNs may lead to the production of sulfidopeptide LTs, which, in turn, could alter microvascular permeability.
Mcmurdo
L
L
Departments of Internal Medicine and Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis. Missouri, USA.
Stephenson
A H
AH
Baldassare
J J
JJ
Sprague
R S
RS
Lonigro
A J
AJ
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D002417:Cattle; D002450:Cell Communication; D006801:Humans; D017572:Leukotriene A4 / Q000378:metabolism; D015289:Leukotrienes / Q000096:biosynthesis* / Q000378:metabolism; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*
D017572:Leukotriene A4; D015289:Leukotrienes; D001094:Arachidonate 5-Lipoxygenase