Mannose-Binding Lectin Is a Regulator of Inflammation That Accompanies Myocardial Ischemia and Reperfusion Injury

• Published in: The Journal of immunology (1950) 2005-07, Vol.175 (1), p.541-546
• Main Authors: Walsh, Mary C, Bourcier, Todd, Takahashi, Kazue, Shi, Lei, Busche, Marc N, Rother, Russell P, Solomon, Scott D, Ezekowitz, R. Alan B, Stahl, Gregory L
• Format: Article
• Language: English
• Subjects: Animals; Complement C1q - deficiency; Complement C1q - genetics; Complement C2 - deficiency; Complement C2 - genetics; Complement Factor B - deficiency; Complement Factor B - genetics; Complement Factor D - deficiency; Complement Factor D - genetics; Complement Pathway, Alternative; Complement Pathway, Classical; Complement Pathway, Mannose-Binding Lectin; Inflammation - etiology; Inflammation - immunology; Inflammation Mediators - metabolism; Male; Mannose-Binding Lectin - deficiency; Mannose-Binding Lectin - genetics; Mannose-Binding Lectin - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardial Reperfusion Injury - etiology; Myocardial Reperfusion Injury - immunology; Myocardial Reperfusion Injury - prevention & control
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.175.1.541

The mannose-binding lectin (MBL), a circulating pattern recognition molecule, recognizes a wide range of infectious agents with resultant initiation of the complement cascade in an Ab-independent manner. MBL recognizes infectious non-self and altered self in the guise of apoptotic and necrotic cells. In this study, we demonstrate that mice lacking MBL, and hence are devoid of MBL-dependent lectin pathway activation but have fully active alternative and classical complement pathways, are protected from cardiac reperfusion injury with resultant preservation of cardiac function. Significantly, mice that lack a major component of the classical complement pathway initiation complex (C1q) but have an intact MBL complement pathway, are not protected from injury. These results suggest that the MBL-dependent pathway of complement activation is a key regulator of myocardial reperfusion ischemic injury. MBL is an example of a pattern recognition molecule that plays a dual role in modifying inflammatory responses to sterile and infectious injury.