Dl. Laskin et Kj. Pendino, MACROPHAGES AND INFLAMMATORY MEDIATORS IN TISSUE-INJURY, Annual review of pharmacology and toxicology, 35, 1995, pp. 655-677
Tissue injury induced by a diverse group of xenobiotics appears to inv
olve both direct and indirect damage to target cells. Thus, while chem
icals may act directly on target cells resulting in toxicity, they may
also act indirectly by recruiting and activating resident and inflamm
atory tissue macrophages. Macrophages are potent secretory cells that
release an array of mediators, including proinflammatory and cytotoxic
cytokines and growth factors, bioactive lipids, hydrolytic enzymes, r
eactive oxygen intermediates, and nitric oxide-each of which has been
implicated in the pathogenesis of tissue injury, The potential role of
macrophages and their mediators in tissue injury has been extensively
investigated in the lung and the liver. In both of these tissues, xen
obiotics induce localized macrophage accumulation and mediator release
. Furthermore, when macrophage functioning is blocked, pulmonary and h
epatic injury-induced agents such as ozone, bleomycin, acetaminophen,
carbon tetrachloride, and galactosamine are reduced. These data provid
e direct support for the hypothesis that macrophages and the mediators
they release contribute to xenobiotic-induced tissue injury.