Mannose-binding lectin is a regulator of inflammation that accompanies myocardial ischemia and reperfusion injury.
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.
Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, Harvard Medical School, Boston MA 02115, USA.
Mary C
MC
Walsh
Todd
T
Bourcier
Kazue
K
Takahashi
Lei
L
Shi
Marc N
MN
Busche
Russell P
RP
Rother
Scott D
SD
Solomon
R Alan B
RA
Ezekowitz
Gregory L
GL
Stahl
D000818:Animals; D015922:Complement C1q / Q000172:deficiency / Q000235:genetics; D003175:Complement C2 / Q000172:deficiency / Q000235:genetics; D011415:Complement Factor B / Q000172:deficiency / Q000235:genetics; D011416:Complement Factor D / Q000172:deficiency / Q000235:genetics; D003170:Complement Pathway, Alternative; D003171:Complement Pathway, Classical; D037582:Complement Pathway, Mannose-Binding Lectin; D007249:Inflammation / Q000209:etiology* / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D037601:Mannose-Binding Lectin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015428:Myocardial Reperfusion Injury / Q000209:etiology* / Q000276:immunology* / Q000517:prevention & control
D003175:Complement C2; D018836:Inflammation Mediators; D037601:Mannose-Binding Lectin; D015922:Complement C1q; D011416:Complement Factor D; C493491:complement factor D, mouse; D011415:Complement Factor B