Platelet-associated CD40/CD154 mediates remote tissue damage after mesenteric ischemia/reperfusion injury

• Published in: PloS one Vol. 7; no. 2; p. e32260
• Main Authors: Lapchak, Peter H, Ioannou, Antonis, Kannan, Lakshmi, Rani, Poonam, Dalle Lucca, Jurandir J, Tsokos, George C
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.02.2012; Public Library of Science (PLoS)
• Subjects: Animals; Apoptosis; Atherosclerosis; B cells; Biology; Blood platelets; Blood Platelets - cytology; Blood Platelets - metabolism; Cardiovascular disease; CD40 antigen; CD40 Antigens - genetics; CD40 Antigens - physiology; CD40 Ligand - genetics; CD40 Ligand - physiology; CD40L protein; Complement System Proteins; Damage; Endotoxins - metabolism; Female; Image Processing, Computer-Assisted; Immunohistochemistry - methods; Inflammation; Inflammatory bowel disease; Injuries; Intestine; Intestines - pathology; Ischemia; Ligands; Lung - pathology; Lung diseases; Lungs; Male; Medical schools; Medicine; Mice; Mice, Inbred C57BL; Models, Biological; Neutrophils; Oxidative stress; Pathogenesis; Platelets; Reperfusion; Reperfusion Injury - metabolism; Rheumatology; Rodents; Stroke; Thromboembolism; Time Factors; Trends; United States > US; Massachusetts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0032260

Several innate and adaptive immune cell types participate in ischemia/reperfusion induced tissue injury. Amongst them, platelets have received little attention as contributors in the process of tissue damage after ischemia reperfusion (I/R) injury. It is currently unknown whether platelets participate through the immunologically important molecules including, CD40 and when activated, CD154 (CD40L), in the pathogenesis of I/R injury. We hypothesized that constitutive expression of CD40 and activation-induced expression of CD154 on platelets mediate local mesenteric and remote lung tissue damage after I/R injury. Wild type (WT; C57BL/6J), CD40 and CD154 deficient mice underwent mesenteric ischemia for 30 minutes followed by reperfusion for 3 hours. WT mice subjected to mesenteric I/R injury displayed both local intestinal and remote lung damage. In contrast, there was significantly less intestinal damage and no remote lung injury in CD40 and CD154 deficient mice when compared to WT mice. Platelet-depleted WT mice transfused with platelets from CD40 or CD154 deficient mice failed to reconstitute remote lung damage. In contrast, when CD40 or CD154 deficient mice were transfused with WT platelets lung tissue damage was re-established. Together, these findings suggest that multiple mechanisms are involved in local and remote tissue injury and also identify platelet-expressed CD40 and/or CD154 as mediators of remote tissue damage.