P.G.M. Bloemen

Adhesion molecules: a new target for immunoliposome-mediated drug delivery

The anti‐ICAM‐1 monoclonal antibody F10.2 was conjugated to liposomes to target to cells expressing the cell adhesion molecule ICAM‐1. We demonstrate that F10.2 immunoliposomes bind to human bronchial epithelial cells (BEAS‐2B) and human umbilical vein endothelial cells (HUVEC) in a specific, dose‐ and time‐dependent manner. It appears that the degree of ICAM‐1 expression is the limiting factor in the degree of immunoliposome binding to the cells. These results are a first step in the strategy for specific drug delivery to target sites characterised by increased expression of adhesion molecules.

Cellular uptake of liposomes targeted to intercellular adhesion molecule-1 (ICAM-1) on bronchial epithelial cells

Previously, it was demonstrated that immunoliposomes, bearing anti-intercellular adhesion molecule-1 (ICAM-1) antibodies (mAb F10.2), can specifically bind to different cell types expressing ICAM-1. In this study, we have quantified the amount of immunoliposomes binding to IFN-gamma activated human bronchial epithelial cells (BEAS-2B) in vitro and studied the subsequent fate of cell-bound anti-ICAM-1 immunoliposomes. We demonstrate that binding of the immunoliposomes to the epithelial cells depends on the liposome concentration used. After binding to the cell surface, the anti-ICAM-1 immunoliposomes are rapidly internalised by the epithelial cells. Sixty percent of cell-bound immunoliposomes were internalised by the epithelial cells within 1 h of incubation at 37 degrees C. The results indicate that ICAM-1 targeted immunoliposomes may be used as carriers for the intracellular delivery of anti-inflammatory drugs to sites of inflammation characterised by an increased expression of ICAM-1.

THE LINOLEIC ACID METABOLITE 13-HODE MODULATES DEGRANULATION OF HUMAN POLYMORPHONUCLEAR LEUKOCYTES

The effect of the linoleic acid metabolite 13‐hydroxyoctadecadienoic acid (13‐HODE) on degranulation of human polymorphonuclear leukocytes (PMNs) was investigated by measuring the expression of CD11b and CD67 on the plasma membrane. 13‐HODE (5 μM) by itself induced degranulation of PMNs, but to a lesser extent as compared to PAF and fMLP. In addition, 13‐HODE was found to inhibit the PAF‐induced degranulation whereas an additive effect on the fMLP‐induced PMNs degranulation was observed. These results indicate that 13‐HODE can play a modulatory role in degranulation of PMNs.