Cellular distribution of 5-lipoxygenase and leukotriene receptors in postsurgical peritoneal wound repair.
Products of the eicosanoid pathways, namely prostaglandins and leukotrienes, are known to play a key role in inflammatory and immune responses, as well as other wound cellular activities of wounded tissue. The objective of this study was to determine whether surgically induced intraperitoneal and incisional wounds in the rat express 5-lipoxygenase and contain binding sites for leukotrienes and whether their levels change during the course of healing. With the use of a specific monoclonal antibody generated against 5-lipoxygenase, the enzyme was immunohistochemically localized in various wound cells during postsurgical days 2 to 35. The inflammatory cells within the wound were the major cell types containing 5-lipoxygenase immunoreactive protein, followed by fibroblasts in the incisional and peritoneal fibrous adhesions, striated muscle, and the vasculature. The greatest level of immunostaining was observed during the first 2 weeks after surgery, which decreased to near unwounded levels by day 35. Light microscope autoradiographic binding studies using (3)H-leukotrienes indicated that the peritoneal/incisional wounds and unwounded tissues contain specific (3)H-leukotriene C(4) and (3)H-leukotriene D(4) but not (3)H-leukotriene B(4) binding sites. Quantitative grain analysis (net grain density/100 microm(2)), representing specific (3)H-leukotriene C(4) and (3)H-leukotriene D(4) binding sites calculated for different cell types in the wound and unwounded regions showed that (3)H-leukotriene C(4) binding was highest over the striated muscle proximal to the injury and incisional and peritoneal granulation tissue fibroblasts. The net grain density over these cells increased by 3-, 2.5-, and 2-fold by day 14, respectively, and declined to the control values by day 21 after injury (p < 0.05). The pattern of (3)H-leukotriene D(4) binding was similar to that observed for (3)H-leukotriene C(4), but with a lower density. The grain density for (3)H-leukotriene C(4) and (3)H-leukotriene D(4) in arteriolar endothelial and smooth muscle cells remained unchanged. These data suggest that the products of the lipoxygenase pathway through the presence of their specific receptors may play an important role in peritoneal wound repair and adhesion formation.
Chegini
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Institute for Wound Research, Department of Obstetrics and Gynecology, University of Florida, Gainesville, FL 32610, USA.
Rossi
M J
MJ
Holmdahl
L
L