C1q is the recognition subunit of the first component of the classical complement pathway. It participates in clearance of immune complexes and apoptotic cells as well as in defense against pathogens. Inappropriate activation of the complement contributes to cellular and tissue damage in different pathologies, urging the need for the development of therapeutic agents that are able to inhibit the complement system. In this study, we report heme as an inhibitor of C1q. Exposure of C1q to heme significantly reduced the activation of the classical complement pathway, mediated by C-reactive protein (CRP) and IgG. Interaction analyses revealed that heme reduces the binding of C1q to CRP and IgG. Furthermore, we demonstrated that the inhibition of C1q interactions results from a direct binding of heme to C1q. Formation of complex of heme with C1q caused changes in the mechanism of recognition of IgG and CRP. Taken together, our data suggest that heme is a natural negative regulator of the classical complement pathway at the level of C1q. Heme may play a role at sites of excessive tissue damage and hemolysis where large amounts of free heme are released.
Latent fingermark morphology was examined over a period of approximately two months. Variation in topography was observed with atomic force microscopy and the expansion of the fingermark occurred in the form of the development of an intermediate area surrounding the main fingermark ridge. On an example area of a fingermark on silicon, the intermediate region exists as a uniform 4nm thick deposit; on day 1 after deposition this region extends approximately 2μm from the edge of the main ridge deposit and expands to a maximum of ∼4μm by day 23. Simultaneously the region breaks up, the integrity is compromised by day 16, and by day 61 the area resembles a series of interconnected islands, with coverage of approximately 60%. Observation of a similar immediate area and growth with time on surfaces such as Formica was possible by monitoring the mechanical characteristics of the fingermark and surfaces though phase contrast in tapping mode AFM. The presence of this area may affect fingermark development, for example affecting the gold distribution in vacuum metal deposition. Further study of time dependence and variation with donor may enable assessment of this area to be used to evaluate the age of fingermarks.
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