CD40-CD40 ligand disruption does not prevent hyperoxia-induced injury.
Recent studies suggest that apoptosis plays a role in oxygen-induced injury, although the activation pathways and the executioner proteases that lead to cleavage of lung cell proteins and DNA, are not yet identified. We explored previously the tumor necrosis factor/tumor necrosis factor receptor and the Fas/FasL, belonging to the intrinsic pathway, and could not demonstrate any protective effect by interfering with these cell receptors. Lately, it has been shown that interacting with the CD40 system, also known to promote cell death, by administering anti-CD40 ligand (L) antibody was beneficial in several diseases and, in particular, in hyperoxia-induced injury. Using CD40- and CD40L-deficient mice (-/-) as well as administering anti-CD40L antibody, we examined the extent of lung injury in oxygen-breathing mice by several ways (lung weight, histology, inflammatory mediators, and DNA ladder) as well as the mortality. The development of lung injury was similar in wild-type, CD40-/-, CD40L-/-, or in wild-type mice treated with anti-CD40L antibody. Apoptosis was present in all conditions at 72 hours of oxygen exposure. These results show that oxygen-induced injury does not require CD40-CD40L interaction and that apoptosis of lung cells does not involve this pathway.
Barazzone Argiroffo
Constance
C
Department of Pediatrics, University of Geneva Medical School, Geneva, Switzerland. constance.barrazone@medecine.unige.ch
Donati
Yves R
YR
Boccard
Julien
J
Rochat
Anne F
AF
Vesin
Christian
C
Kan
Chen-Da
CD
Piguet
Pierre-François
PF
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D019013:CD40 Antigens / Q000235:genetics / Q000502:physiology*; D023201:CD40 Ligand / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D016207:Cytokines / Q000032:analysis; D018496:Hyperoxia / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control; D008168:Lung / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
D000906:Antibodies; D019013:CD40 Antigens; D016207:Cytokines; D012333:RNA, Messenger; D023201:CD40 Ligand