Qualitative regional differences in adipose tissue growth and cellularity in male Wistar rats fed ad libitum.

Adipose tissue grows primarily by a combination of increases in fat cell volume (hypertrophy) and in fat cell number (hyperplasia), but the regional growth pattern of white adipose tissue depots in animal species and in the human is still unclear. In this study we characterized fully the age-related changes in adipose tissue growth, composition, and cellularity of four fat depots of male Wistar rats that varied in age from 7 wk to 15 mo and in body weight from 178 to 808 g. Body weight and the weight of each of the four adipose depots studied (epididymal, mesenteric, subcutaneous inguinal, and retroperitoneal) increased progressively with age and ad libitum feeding. Comparison of the cellularity of the four adipose depots, however, showed remarkable and significant differences in the pattern of growth within the same animals. The cumulative growth of the two intraabdominal fat depots (mesenteric and epididymal) was due mostly to hypertrophy (increases in cell volume of 83 and 64%, respectively), whereas the growth of the other two depots (retroperitoneal and inguinal) was due predominantly to hyperplasia (increases in cell number of 58- and 65%, respectively). These findings uncover major and unexpected regional differences in the modulation of adipose tissue growth within aging animals fed ad libitum and suggest local, region-specific regulatory controls of this growth.

High molecular weight transforming growth factor beta is excreted in the urine in active nodular sclerosing Hodgkin's disease.

To measure the in vivo secretion of high molecular weight (HMW) transforming growth factor (TGF)beta by Reed-Sternberg cells from patients with nodular sclerosing Hodgkin's disease, we studied the urine samples from untreated patients. The urinary proteins did not promote the proliferation of NIH-3T3 cells in monolayer culture and contained similar amounts of total TGF activity when compared with normal controls. Urinary proteins from 24 different control and test urines were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. Either of two primary antibodies were used for immunoblot detection: (a) affinity column purified polyclonal anti-TGF beta 1 prepared against platelet TGF beta 1 or (b) monoclonal anti-HMW-TGF beta prepared against HMW-TGF beta secreted by cloned L-428 Reed-Sternberg cells. All patients with active nodular sclerosing Hodgkin's disease had a detectable HMW-TGF beta (approximately 300,000) which cross-reacted with both anti-TGF beta 1 and anti-HMW-TGF beta. Purification demonstrated HMW-TGF beta which was active at physiological pH. Twelve control urine samples from healthy adults and 5 follow-up samples from the Hodgkin's patients after successful treatment contained no detectable urinary HMW-TGF beta. The in vivo production of HMW-TGF beta in untreated nodular sclerosing Hodgkin's disease supports the conclusion that this growth factor is secreted in large amounts by Reed-Sternberg cells or cells stimulated by Reed-Sternberg cells.

Neutralizing antibodies against transforming growth factor beta potentiate the proliferation of Ki-1 positive lymphoma cells. Further evidence for negative autocrine regulation by transforming growth factor beta.

Activated lymphocytes and malignant lymphoma cells derived from them (Ki-1 positive lymphoma cells) share similar mechanisms of proliferation. To further examine the inhibitory role of endogenous transforming growth factor beta (TGF beta) in Ki-1 positive lymphoma cells, the authors studied anti-TGF beta antibodies and measured their effect on proliferation. A monoclonal antibody (T1A5) prepared against a unique antigenic epitope of high molecular weight Hodgkin's TGF beta and a polyclonal rabbit antibody prepared against highly purified 25,000 D porcine platelet TGF beta 1 were used. Both antibodies are shown here to inhibit the biological activity of Hodgkin's TGF beta and to crossreact with their respective antigens in immunoblotting. DNA synthesis by Ki-1 lymphoma cells was increased 138-fold by anti-TGF beta 1 antibody and 262-fold by anti-Hodgkin's TGF beta. Exogenous TGF beta 1 suppression was completely reversed by anti-TGF beta 1 antibody and IL-2-induced proliferation was markedly potentiated (41 fold). L-428 Reed-Sternberg cells secrete physiologically active TGF beta but have fewer than 500 TGF beta receptor sites per cell; no significant proliferative response was measured for either anti-TGF beta 1 or anti-Hodgkin's TGF beta. These results show the suppressive effect of exogenous TGF beta 1 on indolent Ki-1 lymphoma cells and suggest that the endogenous secretion of high molecular weight physiologically active TGF beta is important in maintaining the indolent nature of this low-grade Ki-1 positive lymphoma.