Induction of Acute Pulmonary Inflammation. A Differential Effect of C5 and the 200,000 Molecular Weight Form of Trypsin-activated C5 (C5')

A series of studies was performed in which Syrian golden hamsters were injected intratracheally with 25 to 200 micrograms of highly purified human C5 or the 200,000 molecular weight form of trypsin-activated C5 (C5'). Bronchoalveolar lavage (BAL) was performed 4 h after intratracheal injection, the recovered white cells were counted and differentiated, and the BAL fluid was assayed for in vitro neutrophil chemotactic activity. A significant increase in BAL neutrophils and total BAL cell numbers was evident at 4 h after C5' instillation. In contrast, highly purified native C5 induced no evidence of pulmonary inflammation, even at the highest injection doses studied. Kinetic experiments indicated that hamsters receiving an intratracheal injection of 60 micrograms of C5' per animal demonstrated rapid pulmonary neutrophil infiltration that persisted for 120 to 168 h. Control hamsters receiving intratracheal injections of phosphate-buffered saline (PBS) or 60 micrograms of highly purified C5 did not demonstrate significant neutrophil infiltration. Lung pathology studies revealed neutrophilic alveolitis with intraalveolar and intracapillary neutrophil infiltration in the C5'-treated animals. The BAL fluid obtained from C5'-treated, but not from C5-treated or control hamsters, contained chemotactic factors for neutrophils, which appeared to be unrelated to C5. From these studies we conclude that C5', the 200,000 molecular weight form of protease-activated C5, is capable of mediating an acute inflammatory response in the hamster lung in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)