The effects of overexpression of histamine releasing factor (HRF) in a transgenic mouse model.
BACKGROUND
Asthma is a disease that affects all ages, races and ethnic groups. Its incidence is increasing both in Westernized countries and underdeveloped countries. It involves inflammation, genetics and environment and therefore, proteins that exacerbate the asthmatic, allergic phenotype are important. Our laboratory purified and cloned a histamine releasing factor (HRF) that was a complete stimulus for histamine and IL-4 secretion from a subpopulation of allergic donors' basophils. Throughout the course of studying HRF, it was uncovered that HRF enhances or primes histamine release and IL-13 production from all anti-IgE antibody stimulated basophils. In order to further delineate the biology of HRF, we generated a mouse model.


RESULTS
We constructed an inducible transgenic mouse model with HRF targeted to lung epithelial cells, via the Clara cells. In antigen naïve mice, overproduction of HRF yielded increases in BAL macrophages and statistical increases in mRNA levels for MCP-1 in the HRF transgenic mice compared to littermate controls. In addition to demonstrating intracellular HRF in the lung epithelial cells, we have also been able to document HRF's presence extracellularly in the BAL fluid of these transgenic mice. Furthermore, in the OVA challenged model, we show that HRF exacerbates the allergic, asthmatic responses. We found statistically significant increases in serum and BAL IgE, IL-4 protein and eosinophils in transgenic mice compared to controls.


CONCLUSIONS
This mouse model demonstrates that HRF expression enhances allergic, asthmatic inflammation and can now be used as a tool to further dissect the biology of HRF.
Yeh
Yueh-Chiao
YC
Graduate Institute of Natural Healing Sciences, Nanhua University, Chiayi, Taiwan.
Xie
Liping
L
Langdon
Jacqueline M
JM
Myers
Allen C
AC
Oh
Sun-Young
SY
Zhu
Zhou
Z
Macdonald
Susan M
SM
D000818:Animals; D001249:Asthma / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid; D017931:DNA Primers; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000090324:Tumor Protein, Translationally-Controlled 1; D014598:Uteroglobin / Q000235:genetics
D014408:Biomarkers, Tumor; D017931:DNA Primers; C556389:SCGB1A1 protein, human; C556390:Scgb1a1 protein, mouse; D000090324:Tumor Protein, Translationally-Controlled 1; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D014598:Uteroglobin