Integrin avbeta3 acts downstream of insulin in normalization of interstitial fluid pressure in sepsis and in cell-mediated collagen gel contraction

摘要

First published June 13, 2008; doi:10.1152/ajpheart.00161.2008.-The administration of insulin is recommended to patients with severe sepsis and hyperglycemia. Previously, we demonstrated that insulin may have direct anti-inflammatory properties and counteracted fluid losses from the circulation by normalizing the interstitial fluid pressure (PnO- P_(IF) is one of the Starling forces determining fluid flux over the capillary wall, and a lowered P_(IF) is one of the driving forces in early edema formation in inflammatory reactions. Here we demonstrate that insub'n restores a lipopolysaccharide (LPS)-lowered P_(IF) via a mechanism involving integrin alpha_(IF). In C57 black mice (n = 6), LPS lowered P_(IF) from -0.2 +- 0.2 to -1.6 +- 0.3 (P < 0.05) and after insulin averaged -0.8 +- 0.2 mmHg (P - 0.098 compared with after LPS). Corresponding values in wild-type BALB/c mice in = 5) were -0.8 +- 0.1, -2.1 +- 0.3 (P < 0.05), and -0.8 +- 0.3 mmHg (P < 0.05 compared with LPS) after insulin administration. In BALB/c integrin beta3-deficient (beta-) mice (n = 6), LPS lowered P from -0.1 +- 0.2 to -1.5 +- 0.3 mmHg (P < 0.05). Insulin did not, however, restore Pif in these mice (averaged -1.7 +- 0.3 mmHg after insulin administration). Cell-mediated collagen gel contraction can serve as an in vitro model for in vivo measurements of P_(IF)- Insulin induced avbeta3~integrin-dependent collagen gel contraction mediated by C2C12 cells. Our findings suggest a beneficiary effect of insulin for patients with sepsis with regard to the fluid balance, and this effect may in part be due to a normalization of P_(IF) by a mechanism involving the integrin alphavbeta3.glucose-insulin-potassium treatment; tissue fluid balance; inflammation