Preformed angiotensin II is present in human mast cells.
OBJECTIVE
The density of mast cells increases in the myocardium of patients suffering from heart failure. However, their function remains unclear. In this study, preformed angiotensin II (ANG II), a potent growth factor, was found to be contained in, and released by, human mast cells.


METHODS
The human mast cell line (HMC-1) was incubated with 0 to 10(-6) M calcitonin gene-related peptide (CGRP) or culture medium. The expression of renin-angiotensin system mRNA was examined using RT-PCR analysis. ELISA and immunohistochemistry with monoclonal antibody against human ANG II were performed to detect the presence of ANG II in HMC-1. The effect of CGRP on the expression of angiotensinogen mRNA was examined by quantitative RT-PCR analysis.


RESULTS
Preformed ANG II was detected in a human mast cell line (HMC-1) which is a neoplastic cell line of mast cells by ELISA and immunohistochemistry. Presence of mRNA of angiotensinogen and renin was confirmed by polymerase chain reaction in HMC-1, while mRNA of angiotensin converting enzyme (ACE) was undetectable. Since myocardial mast cells are interfaced with nerve fibers and functionally associated with CGRP, the effect of CGRP on ANG II release from HMC-1 was examined. CGRP induced the release of ANG II and increased angiotensinogen mRNA in HMC-1.


CONCLUSIONS
The presence of preformed ANG II and gene expression of the renin-angiotensin system were detected in human mast cells. The release and synthesis of ANG II in mast cells was regulated by CGRP.
Hara
Masatake
M
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Ono
Koh
K
Wada
Hiromi
H
Sasayama
Shigetake
S
Matsumori
Akira
A
D000804:Angiotensin II / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007946:Leukemia, Mast-Cell / Q000473:pathology; D008407:Mast Cells / Q000737:chemistry* / Q000187:drug effects; D012333:RNA, Messenger; D011817:Rabbits; D012084:Renin-Angiotensin System / Q000235:genetics
D012333:RNA, Messenger; D000804:Angiotensin II; D015740:Calcitonin Gene-Related Peptide