Drugs that induce neutropenia/agranulocytosis may target specific components of the stromal cell extracellular matrix

The etiology of drug-induced agranulocytosis is poorly understood. Many dru gs that induce neutropenia or agranulocytosis can be metabolized to reactiv e intermediates that covalently bind to macromolecules. Until now, the myel oid precursor cell or an earlier committed progenitor cell has been favoure d as the target for toxicity, due to evidence in some cases of cytotoxic ac tion or antibodies against neutrophils. in the bone marrow, where neutrophi ls mature, certain components of the stromal microenvironment, e.g. intrace llular adhesion molecule 1, vascular cell adhesion molecule 1, CD11b/CD18, heparan sulfate proteoglycans, fibronectin and hemonectin are essential for normal myeloid maturation. This article proposes that drugs implicated in agranulocytosis, or more likely their reactive metabolites, interact with s pecific components of the extracellular matrix and interfere with the norma l regulation of granulopoiesis.