Macrophage targeted response

In this chapter, we will review studies on formulation variables affecting monocyte and macrophage targeting (e.g., size and number of vesicles), in vitro characterization in cell cultures, and in vivo immunomodulation and anti-inflammatory responses. 

Stuehr, D. J., and Nathan, C. F. (1989). Nitric oxide. A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells./. Exp. Med. 169, 1543-1555. 

Table 4 Quaotitmive Skeletal Responses to Macrophage-Targeted Glucocerebroaidase...

S. hi. Rich arris, T A. Olson, and J. m. McPherson Antibody response in patients with Gaucher disease after repealed infusion with macrophage-targeted glucocerehrosidase. 

IV. FIRST DEMONSTRATION OF CLINICAL RESPONSES TO MACROPHAGE-TARGETED GLUCOCEREBROSIDASE... 

Table 2 Hematological Responses to Macrophage-Targeted Glucocerebrosidase Time Course and Effects of Dosage Reduction...

Table 5 Effects of Enzyme Dosage on Hematological and Visceral Responses to Macrophage-Targeted Glucocerebrosidase...

K. A. McKusick, B. R. Rosen, J. Baker, L. T. Niklason, S. C. Hill, S. P. F. Miller, R. O. Brady, and N. W. Barton. Enzyme replacement therapy for Gaucher s disease skeletal responses to macrophage-targeted glucocerebrosidase. Pediatrics 96 629 (1995). 

Badger AM, Newman-Tarr TM, Satterfield JL. Selective immunomodulatory activity of SK F 106615, a macrophage-targeting antiarthritic compound, on antibody and cellular responses in rats and mice. Immunopharmacol 1997 37 53-61. 

The anthrax toxin is a tripartite toxin and consists ofthe binding component protective antigen (PA), the lethal factor (LF), which is a metalloprotease, and the edema factor (EF), which is a calmodulin-dependent adenylyl-cyclase. Both enzyme components are translocated via PA into target cells. PA is activated by furin-induced cleavage and forms heptamers, which are similar to the binding components of C2 toxin and iota toxin. In the low pH compartment of endosomes, the heptamers form pores to allow translocation of LF and EF. LF cleaves six of the seven MEKs (MAPK-kinases) thereby inhibiting these enzymes. The functional consequence is the blockade of the MAPK pathways that control cell proliferation, differentiation, inflammation, stress response, and survival. Whether this is the reason for the LT-induced cell death of macrophages is not clear [1]. 

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