Macrophages and Inflammatory Mediators in Tissue Injury

Abstract

Tissue injury induced by a diverse group of xenobiotics appears to involve both direct and indirect damage to target cells. Thus, while chemicals may act directly on target cells resulting in toxicity, they may also act indirectly by recruiting and activating resident and inflammatory 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, reactive 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, xenobiotics induce localized macrophage accumulation and mediator release. Furthermore, when macrophage functioning is blocked, pulmonary and hepatic injury-induced agents such as ozone, bleomycin, acetaminophen, carbon tetrachloride, and galactosamine are reduced. These data provide direct support for the hypothesis that macrophages and the mediators they release contribute to xenobiotic-induced tissue injury.

Depressant Effects of Ambroxol and Erdosteine on Cytokine Synthesis, Granule Enzyme Release, and Free Radical Production in Rat Alveolar Macrophages Activated by Lipopolysaccharide

“…Inflammatory cytokines released from macrophages play an important role in the regulation of endotoxin-mediated tissue injury (Laskin & Pendino 1995). Ambroxol and erdosteine have been suggested to depress responses of activated phagocytic cells.…”

“…Alveolar macrophages are considered to play a central role in the regulation of immune response to inhaled pathogens and the development of pulmonary inflammation and fibrosis (Laskin & Pendino 1995). Interaction of macrophages with antigens leads to cellular activation, such as cytokine production (Nathan 1987).…”

The hepatic circulation in health and disease: Report of a single-topic symposium

“…47 Pretreating animals with gadolinium chloride, a pharmacological agent that blocks KC function, prevents the tissue injury associated with hepatotoxins such as acetaminophen, carbon tetrachloride, and galactosamine. 48 Which cellular molecules are responsible for mediating this tissue injury? KC and SEC produce NO and TNF-␣ in response to cytokine and endotoxin stimulation, 47 and pretreating animals with the iNOS inhibitor, aminoguanidine, before acetaminophen exposure prevents the early hepatotoxic sequelae.…”

Inhibition of Macrophages With Gadolinium Chloride Alters Intercellular Adhesion Molecule–1 Expression in the Liver During Acute Endotoxemia in Rats

“…These data provide additional support for the hypothesis that macrophages play a role in endotoxin-induced inflammation and tissue injury. 17 Ca 2ϩ /Mg 2ϩ -free Hanks' balanced salt solution containing 0.5 mmol/L ethylene glycol-bis(␤-aminoethyl ether)-N,N-tetraacetic acid and 25 mmol/L HEPES, followed by Leibovitz' s L-15 medium containing 100 U/mL collagenase type IV. Livers were then extracted, weighed, and combed, and the resulting cell suspension filtered through 60-µm nylon mesh (TETKO, Briarcliff Manor, NY).…”