Prepro-endothelin-1 mRNA and its mature peptide in human appendix.
Because the precise immunopathological events occurring in appendicitis are not completely understood, possible local production of endothelin-1 (ET-1) in human appendix was investigated. We used immunohistochemistry and in situ hybridization to detect the presence, distribution, and phenotype of ET-1-positive cells and prepro-ET-1 (pp-ET-1) mRNA-expressing cells. ET-1-positive stromal cells and pp-ET-1 mRNA-expressing cells were detected with different distributions and relative frequencies in normal control appendix, histologically normal appendix, and inflamed appendix. Six of 20 histologically normal appendixes from patients with a clinical diagnosis of acute appendicitis had many ET-1-positive stromal cells and high pp-ET-1 mRNA expression, similar to inflamed appendix. Forty percent of the pp-ET-1 mRNA-expressing cells were neutrophils, and the other positive cells were mast cells and macrophages. We suggest that local production of ET-1 by neutrophils and other inflammatory cells could be a molecular sign of focal inflammation in histologically normal appendixes and that ET-1 could be implicated, with other cytokines, in the pathogenesis of appendicitis by inducing appendiceal ischemia through vasoconstriction.
Massai
Lauretta
L
Department of Anatomical and Biomedical Sciences, University of Siena, 53100 Siena, Italy.
Carbotti
Paola
P
Cambiaggi
Caterina
C
Mencarelli
Marzia
M
Migliaccio
Pierluigi
P
Muscettola
Michela
M
Grasso
Giovanni
G
D001064:Appendicitis / Q000473:pathology; D001065:Appendix / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D019332:Endothelin-1; D016232:Endothelins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008264:Macrophages / Q000473:pathology; D008407:Mast Cells / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D010455:Peptides / Q000378:metabolism; D010641:Phenotype; D011498:Protein Precursors / Q000096:biosynthesis*; D015347:RNA Probes; D012333:RNA, Messenger / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019332:Endothelin-1; D016232:Endothelins; D010455:Peptides; D011498:Protein Precursors; D015347:RNA Probes; D012333:RNA, Messenger