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Asbestos-Induced Pleural Inflammation in Mice Genetically Selected for Maximum or Minimum Inflammatory Response

Pulmonary Division - Heart Institute (InCor), University of Sao Paulo, Brazil

PURPOSE: Asbestos fibers injected into the pleural space induce pleural inflammation by activation of macrophages and neutrophils, leading to apoptosis, cell proliferation, fibrosis and eventually the tumor mesothelioma. The degree of the local inflammatory response may play a role in the overall injury induced by asbestos. We investigated if crocidolite asbestos, a toxic mineral fiber, would produce different degrees of inflammation in mice genetically selected for minimum (AIRmin) or maximum (AIRmax) acute inflammatory response.

METHODS: Three groups of 5 mice were injected intrapleurally with 3 ug/cm2 crocidolite (Cro) asbestos (Control, AIRmin or AIRmax) and one control group with wollastonite (Wol). After 1, 2 or 3 months the animals were sacrificed, the thorax was removed and the lungs expanded and fixed in formalin. The specimens were paraffin embedded and the three more representative transversal sections were stained with HE and analyzed for the presence of inflammatory infiltrate, giant cell reaction, mesothelial cell proliferation, fibrosis and macrophage infiltrate. A score (0-4) was attributed to evaluate the morphological findings: 0: none; 1: slight; 2: mild; 3: moderate; 4: intense. Statistics: ANOVA on Ranks.

RESULTS: Inflammatory Infiltrate: Cro Control, Airmax and AIRmin at all times vs. Wol (*p< 0.05); GCR: AIRmax and AIRmin vs. Wol at all times (*p< 0.05); AIRmax vs. Cro Control at 1mo. (#p< 0.05).

CONCLUSION: All groups of crocidolite-injected mice had more inflammatory infiltrate and giant cell reaction than wollastonite-injected animals at all time-points. No difference was found among subgroups of the crocidolite-injected animals. The giant cell reaction was more evident in animals with maximum inflammatory response in the first month in comparison to crocidolite control animals. Mesothelial cell proliferation, fibrosis and macrophage infiltrate were not different among groups.

CLINICAL IMPLICATIONS: Determination of the crocidolite-associated inflammatory pleural reaction may be significant in understanding the pathogenesis of asbestos-related pleural diseases, including the tumor mesothelioma.

Inflammatory Infiltrate Giant Cell Reaction Cro 1mo. 2mo. 3mo. 1mo. 2mo. 3mo. Control 2.0 ± 0.0 1.3 ± 0.6 2.0 ± 00 0.3 ± 0.6# 0.7 ± 0.6 0.7 ± 0.6 AIRMin 2.0 ± 1.1 2.0 ± 0.9 1.9 ± 0.8 1.3 ± 0.5 1.1 ± 0.6 1.3 ± 0.9 AIRMax 2.7 ± 1.2 2.6 ± 1.0 2.5 ± 1.4 2.7 ± 1.2 1.7 ± 0.9 1.3 ± 1.1 Wol 0.2 ± 0.4* 0.3 ± 0.5* 0.5 ± 0.3* 0.0 ± 0.0* 0.0 ± 0.0* 0.0 ± 0.0*

DISCLOSURE: E. Marchi, None.