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.
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.
Piguet
P F
PF
Department of Pathology, University of Geneva, Switzerland.
Tacchini-Cottier
F
F
Vesin
C
C
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001792:Blood Platelets / Q000166:cytology / Q000276:immunology; D001842:Bone and Bones / Q000276:immunology / Q000378:metabolism*; D018821:CD18 Antigens; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D005260:Female; D016023:Integrins / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008854:Microscopy, Electron; D010976:Platelet Count; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics
D000906:Antibodies; D018821:CD18 Antigens; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen