Laminin concentration in ascites of patients with hepatic cirrhosis and peritoneal carcinomatosis

Laminin levels in ascitic fluid have been proposed as a marker for neoplastic ascites. We compared the concentration of laminin in serum and in ascitic fluid from patients with hepatic cirrhosis and peritoneal carcinomatosis and assessed the diagnostic value of serum laminin levels in differentiating neoplastic from benign ascites. Laminin concentrations were determined by ELISA with antibodies against laminin extracted from the human placenta, in patients with ascites due to peritoneal carcinomatosis (N = 20) and hepatic cirrhosis (N = 33). Patients with infected or hemorrhagic ascites were excluded. The receiver operating characteristic curve was used to determine the sensitivity and specificity of serum laminin for the diagnosis of neoplastic ascites. When compared to the group with cirrhosis, the carcinomatosis group presented significantly higher mean laminin levels in serum (3.3 ± 0.5 vs 2.1 ± 0.4 æg/ml, mean ± SD, P < 0.05) and ascites (2.8 ± 0.5 vs 1.6 ± 0.4 æg/ml, P < 0.05). Although laminin concentration was higher in serum than in ascites, the laminin serum/ascites ratio and serum-ascites gradient did not differ between the studied groups. A significant correlation (r = 0.93, P < 0.0001) was observed between the serum and ascites laminin values. Serum laminin levels >2.25 æg/ml showed 100 percent sensitivity and 73 percent specificity for the diagnosis of neoplastic ascites. Serum concentration seems to be the main determinant of laminin levels in ascitic fluid and its values can be used as a diagnostic parameter in the study of neoplastic ascites.

Laminin/VLA-6 interactions and T cell function

A growing number of investigators consider extracellular matrix (ECM) proteins to be determinant factors in lymphocyte positioning and activation. One major ECM component is laminin, which is constitutively expressed in the thymus as well as in thymus-dependent areas of peripheral lymphoid organs. In the thymus, laminin is produced by epithelial and dendritic cells, and appears to mediate interactions with thymocytes through specific laminin receptors, in particular the integrin VLA-6. This receptor is also expressed by peripheral T cells, and is apparently involved in effector T cell migration and activation. We showed that CD4+ T lymphocytes from chronic chagasic mice exhibited an increase in the absolute and relative number of cells with high VLA-6 expression. Additionally, it is likely that VLA-6/laminin interactions are required for the development of the CD4+ T cell-dependent anti-myocardial autoreactive process that occurs in these animals. Lastly, laminin can bind to some cytokines, a fact that may represent an additional mechanism by which this extracellular matrix component modulates the behavior of T lymphocytes. Taken together, the present data strongly indicate that interactions involving laminin and VLA-6 are functionally linked to relevant events in T cell physiology, comprising entrance of pro-thymocytes into the thymus, intrathymic T cell migration and differentiation, as well as the functioning of mature T lymphocytes, including effector cells.