Eotaxin/CCL11 expression by infiltrating macrophages in rat heart transplants during ongoing acute rejection.
Eotaxin/CCL11 chemokine is expressed in different organs, including the heart, but its precise cellular origin in the heart is unknown. Eotaxin is associated with Th2-like responses and exerts its chemotactic effect through the chemokine receptor-3 (CCR3), which is also expressed on mast cells (MC). The aim of our study was to find the cellular origin of eotaxin in the heart, and to assess whether expression is changing during ongoing acute heart transplant rejection, indicating a correlation with mast cell infiltration which we observed in a previous study. In a model of ongoing acute heart transplant rejection in the rat, we found eotaxin mRNA expression within infiltrating macrophages, but not in mast cells, by in situ-hybridization. A five-fold increase in eotaxin protein in rat heart transplants during ongoing acute rejection was measured on day 28 after transplantation, compared to native and isogeneic control hearts. Eotaxin concentrations in donor hearts on day 28 after transplantation were significantly higher compared to recipient hearts, corroborating an origin of eotaxin from cells within the heart, and not from the blood. The quantitative comparison of eotaxin mRNA expression between native hearts, isografts, and allografts, respectively, revealed no statistically significant difference after transplantation, probably due to an overall increase in the housekeeping gene's 18S rRNA during rejection. Quantitative RT-PCR showed an increase in mRNA expression of CCR3, the receptor for eotaxin, during ongoing acute rejection of rat heart allografts. Although a correlation between increasing eotaxin expression by macrophages and mast cell infiltration is suggestive, functional studies will elucidate the role of eotaxin in the process of ongoing acute heart transplant rejection.
Zweifel
Martin
M
Department of Cardiology, Heart Transplant-Research Laboratory, Swiss Cardiovascular Center, University Hospital Bern, Switzerland. martin.zweifel@doctors.org.uk
Mueller
Christoph
C
Schaffner
Thomas
T
Dahinden
Clemens
C
Matozan
Katja
K
Driscoll
Robert
R
Mohacsi
Paul
P
D000818:Animals; D054413:Chemokine CCL11 / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D017403:In Situ Hybridization; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction
D054413:Chemokine CCL11; D012333:RNA, Messenger