Am. J. Respir. Cell Mol. Biol., Vol 12, No. 2, Feb 1995, 227-231.
Administration of anti-TNF-alpha or anti-CD11a antibodies to normal adult mice decreases lung and bone collagen content: evidence for an effect on platelet consumption
PF Piguet, F Tacchini-Cottier and C Vesin
Department of Pathology, University of Geneva, Switzerland.
Administration of anti-tumor necrosis factor-alpha (anti-TNF-alpha) or
anti-CD11a (LFA-1) antibodies to normal adult mice for about 10 days
markedly decreased the hydroxyproline content in lung and femur. Similar
observation was made using the recombinant soluble TNF receptor (rsTNFR) as
tumor necrosis factor-alpha (TNF-alpha) antagonist. This decrease in
collagen content was most likely due to a decrease of collagen synthesis,
as evidenced by a decrease of the 3H-proline incorporation in lung and bone
and by a decrease of collagen alpha 1 (I) mRNA levels in the lung RNA. The
localization of labeled platelets in the lung of normal mice was decreased
by anti-TNF-alpha but not by anti-CD11a antibodies. Thrombocytopenia
increases the localization of labeled platelets in the lung, and, in this
condition, both anti-TNF- alpha and anti-CD11a antibodies decreased
pulmonary trapping. TNF-alpha mRNA was detected in the lung of normal adult
mice, suggesting that this cytokine is released in the absence of
inflammation. These results indicate that in vivo, endogenous TNF-alpha
stimulates collagen synthesis, most likely by its influence on platelet
trapping, which appears to involve the platelet CD11a since it is decreased
by anti- CD11a antibody.
