Radioiodinated transforming growth factor-,61 i1) bound to the plasma proteinase inhibitor, a2-macroglobulin (a2M), as determined by chromatography on Superose-6 and native polyacrylamide gel electrophoresis. When a2M conformational change was induced with methylamine, 1"I-TGF-jfl binding significantly increased. Intravenously injected 125I_ TGF-il cleared from the circulation of mice rapidly at first; however, intravascular radioactivity stabilized near 20% of the initial level. At necropsy, radioactivity was recovered predominantly in the liver (65%); however, the density of radioactivity (disintegrations per minute/g organ wt) was highest in the lungs. Markedly different results were obtained with purified 125I-TGF-fll-a2M-methylamine complex. Clearance of the complex occurred as a first-order process with a t11 of 4 min.Greater than 90% ofthe radioactivity was recovered in the liver.The clearance and distribution of 125I-TGF-81-a2M-methylamine were equivalent to those observed with '"I-a2M-methylamine and '"I-a2M-trypsin. The latter two radioligands clear via specific a2M receptors in the liver. Large molar excesses of a2M-trypsin or a2M-methylamine competed with 125I-TGFj01-a2M-methylamine for plasma clearance. Native a2M, which does not bind to the a2M receptor, did not compete. The receptor binding domain of a2M-methylamine was blocked by chemical modification or enzyme treatment. The resulting a2M preparations still bound 125I-TGF-fll; however, the complexes did not clear when injected intravenously in mice. The studies presented here demonstrate that a2M can mediate the plasma clearance of a growth factor via the a2M receptor system. We propose that a2M, the a2M receptor, and proteinases may function as a concerted system to regulate TGF-ftl activity and the activity of related factors in vivo. (J. Clin. Invest. 1991.

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A 6-year-old spayed female Golden Retriever was examined because of generalized weakness and abdominal distention. Abdominal ultrasonography revealed a large quantity of peritoneal fluid. In addition, the liver appeared larger than normal and contained multiple, small, nodular masses and cyst-like structures. Abdominal exploratory surgery was performed, and 5 L of serosanguineous peritoneal fluid was removed. Gross lesions were not found in the stomach, kidneys, intestines, adrenal glands, or urinary bladder. There were diffuse cystic nodules in all liver lobes. The dog did not recover from anesthesia. A diagnosis of peliosis hepatis was made on the basis of gross and histologic appearance of the liver. A polymerase chain reaction assay revealed Bartonella henselae DNA in liver specimens. To our knowledge, this is the first report of molecular evidence of B henselae infection in a dog with peliosis hepatis.

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