Mass, number and size of lung fibres in the pathogenesis of asbestosis in sheep.

After long-term asbestos inhalation, the lung tissue burden is much less for chrysotile (CHRY) than for crocidolite (CRO) exposure. Nonetheless CHRY does not appear to be less fibrogenic. To study mechanisms responsible for the low retention of CHRY and the relationships with fibrogenesis, 15 sheep received a single intratracheal injection of either CHRY or CRO. Exposures in 100 ml saline consisted of 100 mg of 1-micron latex beads for the five control sheep, 100 mg UICC CRO fibres for the five CRO sheep and 100 mg UICC B CHRY fibres for the five CHRY sheep. Bronchoalveolar lavage (BAL) was carried out at months 2, 4, 6 and 8 after exposure and necropsy at month 8. BAL and tissue samples were analysed for fibres by transmission electron microscopy. At month 2, mass concentration in BAL was 108 +/- 30 ng/ml for CRO and 0.6 +/- 0.1 ng/ml for CHRY. BAL CRO decreased afterward but BAL CHRY did not. The mass concentration in the lung at month 8 was 40.6 +/- 8.7 ng/mg dry tissue for CRO and 11.5 +/- 7.0 ng/mg for CHRY. BAL fibrogenic activity at month 8 assessed by macrophage fibronectin production was less than 0.2 ng/10(6) cells/24 h in control sheep, 5 +/- 2 in CRO sheep and 11 +/- 2 in CHRY sheep (P less than 0.05 CRO vs CHRY). Histologic score of tissue injury fibrosis was 0 in control sheep, 1.9 +/- 0.3 in CRO sheep and 2.8 +/- 0.1 in CHRY sheep (P less than 0.05). At necropsy, the number size distribution of fibres per microgram of tissue from the (CRO)/(CHRY) sheep was respectively: (127 +/- 54)/(15 +/- 14) for fibres less than 5 microns, (18 +/- 17)/(32 +/- 14) for fibres greater than 5 microns, (1.6 +/- 8)/(7 +/- 13) for fibres greater than 20 microns. This study documented that the low pulmonary retention of CHRY was largely related to the faster alveolar clearance rate of CHRY mass. Fibrogenicity of CHRY remained higher and appeared to be related at least in part to the preferential retention of long and very long CHRY fibres.