Cardiovascular activating factors from the pancreas

Physiological shock elevates plasma levels of factors that activate cardiovascular cells, compromising microvascular functions. The nature and source of these plasma-derived activators are unknown. To examine their possible origin, rat internal organs were homogenized and measured for activity on naive human leukocytes. Tissue samples from visceral organs were homogenized and their ability to induce leukocyte pseudopod formation and nitroblue tetrazolium reduction was tested. A dramatic increase (p<0.001) in leukocyte activation compared to controls was observed with pancreas but not with homogenate from other organs. Activity from the pancreas was isolated using homogenized pancreas, step-wise eluted through Sep-Pak cartridges. Elution fractions were gradient eluted through an HPLC column and characterized for biological activity in vitro and in vivo. Several eluted pancreatic fractions contained leukocyte activators and depressed mean arterial pressure. Some of these activators are of low molecular weight and may be previously unknown, including two which have a mass of 149 and 288 Da. Low molecular-weight factors with high activity are present in pancreatic extracts, and may provide a source for production of potent cell activators capable of inducing inflammatory responses and shock.