Involvement of CD40-CD40L signaling in postischemic lung injury

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 283; no. 6; pp. 1255 - L1262
• Main Authors: Moore, Timothy M, Shirah, W. Bradley, Khimenko, Pavel L, Paisley, Peyton, Lausch, Robert N, Taylor, Aubrey E
• Format: Journal Article
• Language: English
• Published: United States 01.12.2002
• Subjects: Animals; CD40 Antigens - physiology; CD40 Ligand - physiology; In Vitro Techniques; Interleukin-10 - pharmacology; Interleukin-10 - physiology; Ischemia - complications; Ischemia - pathology; Ischemia - physiopathology; Lung - pathology; Lung - physiopathology; Male; Pneumonia - etiology; Pneumonia - pathology; Pneumonia - physiopathology; Pulmonary Circulation; Rats; Rats, Inbred Strains; Recombinant Proteins - pharmacology; Reperfusion Injury - complications; Reperfusion Injury - pathology; Reperfusion Injury - physiopathology; Signal Transduction - physiology
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00016.2002

Department of Physiology, University of Alabama College of Medicine, Mobile, Alabama 36688-0002 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. inflammation; filtration coefficient; lymphocytes; macrophage inflammatory protein-2