Ultraviolet-B Recruits Mannose-Binding Lectin into Skin from Non-Cutaneous Sources11Portions of this work were presented at the 2003 Annual Scientific Sessions of the Society for Investigative Dermatology and published in abstract form: Mannose binding lectin in UV-irradiated skin. J Invest Dermatol 121:77, 2003 (abstr).

Abstract

Mannose-binding lectin (MBL) is an integral part of the innate immune system and functions as an opsonin by binding to pathogens and certain apoptotic cells to promote their uptake by phagocytes. We recently identified an association of low-producing MBL polymorphisms with adult dermatomyositis (DM). Our model is that MBL deficiency leads to a defect in the clearance of apoptotic debris in the skin, thereby predisposing to photosensitive autoimmune disease. In this study, we sought to determine whether MBL binds within the epidermis, and to determine its source, and potential function of this binding. We demonstrated that the MBL is present in irradiated, but not in non-irradiated skin, and in irradiated skin it is bound to apoptotic keratinocytes (KC). We found that MBL is not made by KC, showing indirectly that it comes from an exogenous source, despite the fact that other complement components are made by KC and upregulated by ultraviolet irradiation. Finally, we demonstrated that non-KC-derived MBL bound to apoptotic KC in vitro and increased the uptake of these cells by dendritic cells. We hypothesize that MBL may facilitate non-inflammatory clearance of apoptotic debris in patients with photosensitive forms of DM.

Immune regulation by fibroblasts in tissue injury depends on uPARAP-mediated uptake of collectins

“…After secretion, soluble defense collagens are found in the circulation, but in many cases, they are also in extravascular compartments. Mannose-binding lectin (MBL), a central blood-borne defense collagen, becomes deposited at injured sites after several types of skin injury, where it acts in the defense against infectious agents as well as in the clearance of apoptotic cells (Lokitz et al, 2005). In the lung, two types of collectins, surfactant proteins D and A (SP-D and SP-A, respectively), are present on mucosal and alveolar surfaces where they play critical roles in innate immune responses (Madan et al, 2001; Wu et al, 2003).…”

Mannose-binding lectin and the balance between immune protection and complication

“…Small amounts of MBL are also synthesized in the kidney, thymus, tonsil, small intestine and vagina, where mRNA has been detected [36–38]. MBL protein has also been found in other organs, such as the skin, brain and lung, although its mRNA has not been detected in those areas [1,19,36,39]. In the lung, MBL is found in the bronchial alveolar lavage of healthy hosts and also on airway smooth muscle following infection [19,40].…”

“…In the lung, MBL is found in the bronchial alveolar lavage of healthy hosts and also on airway smooth muscle following infection [19,40]. In the skin and the brain, MBL is observed only following burn and trauma injury, respectively [19,39,41]. The alveolar space is surrounded by capillaries, suggesting that MBL may traverse these vessels to enter the alveoli.…”

“…In the skin, following UVB exposure, MBL is most likely recruited from local capillaries into damaged sub-epithelial tissue [1,36,39]. In this setting, MBL aids in clearing apoptotic keratinocytes [39]. Our animal burn model studies provide in vivo evidence of MBL involvement in the skin.…”

Molecular defects in the mannose binding lectin pathway in dermatological disease: Case report and literature review

“…Apart from impairing local defenses (potentially facilitating recurrent oral ulcers), low MBL levels allows a more constant pathogenic stimulation, leading to immune cell infiltration and a Th1-type cytokine profile (with increased levels of IL-12 and interferon-γ) [36,37]. In addition, MBL has an important role in clearance of apoptotic cells (MBL is recruited from noncutaneous sources to bind apoptotic keratinocytes and induce their uptake by dendritic cells) [38], the accumulation of which can favor autoimmunity, as the release of intracellular components triggers inflammatory cytokine production and development of reactive clones, leading to autoantibody formation [39,40]. In the specific case of BD, there are large numbers of PMNs located within mucocutaneous lesions, and MBL deficiency contributes to impaired clearance of these cells after they undergo apoptosis, precipitating the immune response described [37].…”