Burn injury reveals altered phenotype in mannan-binding lectin-deficient mice

Abstract

Burn injury destroys skin, the second largest innate immune organ in the body, and triggers chaotic immune and inflammatory responses. The pattern recognition molecule, mannan-binding lectin (MBL), plays an important role in the first-line host defense against infectious agents. MBL initiates the lectin complement pathway and acts as an opsonin. Recent studies suggest that MBL also modulates inflammatory responses. We report that local responses after burn in MBL null mice differ from those found in wild-type (WT) mice in the following important biological markers: spontaneous eschar separation, thinned epidermis and dermis, upregulation of soluble factors including cytokines, chemokines, cell adhesion molecules, a growth factor-binding protein, and matrix metalloproteinases. Mice lacking C1q, C4, or C3 did not show the lack of eschar separation seen in MBL null-burn phenotype. These findings implicate MBL as an important molecule in the maintenance of the homeostatic balance.

Figure 1. Eschars in WT and MBL null mice after burn

(a) Phenotype of MBL null mice and WT mice 20 hours postburn. Histological examination of eschars after 20 hours by hematoxylin and eosin staining; (b) and (c) MBL null mice; (d) WT mice. Normal skin without burn; (e) MBL null mice; and (f) WT mice.

Figure 2. MMP activities in skin after burn

(a) MMP activities (collagenase/gelatinase) were determined at various time points. Numbers of mice used were 4, 6, 6, and 5 for WT mice and 5, 5, 6, and 5 for MBL null mice at no burn and after 2, 5, and 20 hours, respectively. (b) Localization of MMP activity in skin adjacent to burned skin after 20 hours. Original magnification ×20.

Figure 3. Local biological response in burned skin

(a) The increase of molecules in WT as compared with MBL null mice. (b) IL-6 levels in WT and MBL null mice following burn injury. Levels of IL-6 were determined in skin extracts at different time points after the burn injury. Numbers of mice used were 5, 6, 7, and 7 for WT and 5, 3, 5, and 6 for MBL null mice at no burn and after 2, 5 and 20 hours, respectively. Two experiments were combined. The data at 20 hours after burn injury were reported in our previous study (Møller-Kristensen et al., 2006).

Figure 4. Proposed roles of MBL against burn insults

Arrowheads indicate activation and induction. Arrows with blunt heads indicate inhibition and blocking. Names of factors in solid and outlined letters represent inflammatory and non-inflammatory states, respectively.