AJP - Lung Cellular and Molecular Physiology, Vol 261, Issue 2 133-L139, Copyright © 1991 by American Physiological Society
Neutrophil chemoattractant production by cultured serotonin-stimulated bovine and human endothelial cells
A. Charles, S. Rounds and H. W. Farber
Pulmonary Center, Boston University School of Medicine, Massachusetts 02118.
Recent studies have demonstrated that serotonin (5-HT) is avidly taken up
and metabolized by vascular endothelial cells (EC) and have suggested that
5-HT may contribute to inflammatory responses. Because EC can produce
neutrophil cytokines among their biologically active molecules, we
hypothesized that the interaction of 5-HT and EC might cause production of
such a cytokine. Using a modified Boyden chamber assay, we found that
cultured bovine aortic (BA), bovine pulmonary arterial (BPA), and human
umbilical vein (HUV) EC incubated with 5-HT produced a neutrophil
chemoattractant (NCA). The NCA was predominantly chemotactic, was not
stored in an active form, appeared within 5 min of incubation with 5-HT,
and required de novo protein synthesis for its appearance. The mechanism of
NCA production was different in the three types of EC examined. Elaboration
of NCA and BAEC and HUVEC was apparently mediated by 5-HT1 receptors and
did not require uptake of 5-HT, whereas its elaboration from BPAEC required
5-HT uptake and was apparently mediated by 5-HT2 receptors. Incubation with
three different lipoxygenase inhibitors blocked production of NCA, whereas
incubation with a cyclooxygenase inhibitor did not. Further
characterization of the NCA demonstrated that it was a mixture of several
different chemotactic lipids and was distinct from other lipid or
phospholipid neutrophil chemoattractants. These studies suggest that the
interaction of the platelet-release product, 5-HT, with the adjacent
endothelium results in the production of a chemoattractant that could
affect neutrophil accumulation at sites of inflammation.
