A Reaction of the Mouse Spleen Extracellular Matrix to Administration of Liposome-Encapsulated Dextrazide in Stabilization Period of BCG-Induced Inflammation

Abstract

The objective: to study a response of the spleen extracellular matrix (ECM) to the liposome-encapsulated dextrazide (LEDZ) administration in the stabilization period of BCG-induced granulomatosis.Subjects and Methods. A model of generalized tuberculosis inflammation was reproduced by injecting mice with mycobacteria from BCG vaccine (BCG-infected mice). Intact mice served as controls. During inflammation stabilization, the infected mice were dosed with LEDZ by inhalation and intraperitoneal injection, and main ECM components were assessed.Results. The BCG-infected mice showed a decrease in the structural components of proteoglycans (PGs) but demonstrated elevated profibrotic fractions of hydroxyproline (Hyp), enhanced activity of matrix metalloproteinases (MMPs) and no differences in the content of their tissue inhibitors (TIMPs), that indicated the fibrosis of the organ. Despite the way of LEDZ administration, the level of uronic acids in PGs and activity of hyaluronidases increased but the content of protein-bound Hyp was reduced with no differences in the content of free Hyp versus infected untreated mice. The administration of LEDZ by inhalation reduced content of profibrotic fractions of Hyp but increased galactose in PGs increased to the level of control mice. The intraperitoneal LEDZ administration decreased the protein content in PGs.

Keywords

• липосомальная форма декстразида
• туберкулезный гранулематоз
• внеклеточный матрикс селезенки
• гликозаминогликаны
• коллагены
• матриксные металлопротеиназы/тканевые ингибиторы металлопротеина