The differing roles of the classical and mannose-binding lectin complement pathways in the events following skeletal muscle ischemia-reperfusion.
Complement is an important mediator of the injuries observed after skeletal muscle ischemia and subsequent reperfusion. Although the classical pathway had been assumed to be the major pathway of activation leading to injury, the mannose-binding lectin (MBL) pathway might also play a contributing role. In this study, we found that MBL-deficient mice had significant protection after skeletal muscle reperfusion injury compared with wild-type, classical pathway-specific C1q-deficient mice, or MBL-deficient mice reconstituted with recombinant human MBL. MBL-deficient mice, however, were not protected from permeability edema or secondary lung injury after ischemia-reperfusion. These data indicate that blockade of the classical pathway alone (C1q) is protective against permeability edema and remote pulmonary injury but not protective against histologic muscle injury. In contrast, blocking the MBL pathway alone protects against histological injury but is not protective against permeability edema or lung injury. Thus, the activation of both pathways is likely responsible for the full spectrum of injuries observed after skeletal muscle reperfusion injury.
Chan
Rodney K
RK
Department of Surgery and Pediatrics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Ibrahim
Shahrul I
SI
Takahashi
Kazue
K
Kwon
Edwin
E
McCormack
Michael
M
Ezekowitz
Alan
A
Carroll
Michael C
MC
Moore
Francis D
FD
Austen
William G
WG
D000818:Animals; D002199:Capillary Permeability; D015922:Complement C1q / Q000172:deficiency; D003171:Complement Pathway, Classical / Q000502:physiology*; D037582:Complement Pathway, Mannose-Binding Lectin / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D037601:Mannose-Binding Lectin / Q000172:deficiency; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000473:pathology*; D015427:Reperfusion Injury / Q000150:complications / Q000276:immunology*; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000276:immunology; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology / Q000276:immunology*
D037601:Mannose-Binding Lectin; D015922:Complement C1q