Involvement of CD40-CD40L signaling in postischemic lung injury.
Our studies show that ischemia-reperfusion (I/R) in the isolated rat lung causes retention of lymphocytes, which is associated with increased microvascular permeability, as determined by quantitative measurement of the microvascular filtration coefficient (K(f,c)). Immunoneutralization of either CD40 or CD40L, cell surface proteins important in lymphocyte-endothelial cell proinflammatory events, results in significantly lower postischemic K(f,c) values. Antagonism of CD40-CD40L signaling also results in attenuation of I/R-elicited macrophage inflammatory protein-2 production. Rat lymphocytes activated ex vivo with phorbol 12-myristate, 13-acetate increased K(f,c) in isolated lungs independently of I/R, and this increase was prevented by pretreating lungs with anti-CD40. In addition to lymphocyte involvement via CD40-CD40L interactions, our studies also show that I/R injury is potentiated by antagonism of IL-10 produced locally within the postischemic lung, whereas exogenous, rat recombinant IL-10 provided protection against I/R-induced microvascular damage. Thus acute lymphocyte involvement in lung I/R injury involves CD40-CD40L signaling mechanisms, and these events may be influenced by local IL-10 generation.
Moore
Timothy M
TM
Department of Physiology, University of Alabama College of Medicine, Mobile, Alabama 36688-0002, USA.
Shirah
W Bradley
WB
Khimenko
Pavel L
PL
Paisley
Peyton
P
Lausch
Robert N
RN
Taylor
Aubrey E
AE
D000818:Animals; D019013:CD40 Antigens / Q000502:physiology*; D023201:CD40 Ligand / Q000502:physiology*; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000494:pharmacology / Q000502:physiology; D007511:Ischemia / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D008297:Male; D011014:Pneumonia / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D011652:Pulmonary Circulation; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D015427:Reperfusion Injury / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology*
D019013:CD40 Antigens; D011994:Recombinant Proteins; D016753:Interleukin-10; D023201:CD40 Ligand