Although MASP-3 has been reported to have an enzymatic activity towards insulin-like growth factor-binding protein-5, the functional activity of MASP-3 and MAp44 has so far been ascribed primarily to an inhibitory activity on the activation of click here the lectin pathway [10], although very recently an activity of MASP-3 in accelerating cleavage of factor B and factor D has been presented [14]. Conversely, MASP-1 is clearly an active enzyme which may initiate cleavage of several substrates, some being members of the complement system but others belonging more traditionally to other physiological systems, i.e. a thrombin-like activity

in cleaving fibrinogen and factor XIII and the protease activated receptor 4 (PAR4) [13,15,16]. Also of note, the MASP1 gene has been implicated in the aetiology Selleckchem PLX 4720 of the 3MC syndrome, although the mechanism remains unknown [17,18]. An assay for MASP-1 will thus be of importance in a number of scientific fields. The role of MBL was discovered through the study of patients with unexplained susceptibility to infections and opsonin deficiency, as such patients were found to be MBL-deficient [19]. Previously we have described a patient lacking MASP-2, and thus

a functional lectin pathway [20]. It seems plausible that elucidating the role(s) of the MASPs as well as those of the MBL-associated small, non-enzymatic splice products, MAp44 and MAp19 [11,21] may well benefit from epidemiological investigations

on selected patient populations. We thus decided to construct assays for these components. We have presented assays previously for MASP-2, MASP-3, MAp44 and MAp19 [11,21,22]. Similarly, we have generated assays 4��8C for the recognition molecules associating with the MASPs/MBL-associated proteins (Maps), i.e. MBL, H-, L- [23] and M-ficolin [24]. The development of the assay for MASP-1 presented here was hampered by the difficulty in raising selective monoclonal antibodies (mAb) due to the extensive sharing of domains between the proteins of the MASP1 gene, which encodes three alternative splice products giving rise to the three proteins MASP-1, MASP-3 and MAp44 [25]. MASP-1 and MASP-3 share five domains (constituting the so-called A-chain), whereas they have unique protease domains (SP domains or B-chains), and the protein MAp44 shares its first four domains with MASP-1 and MASP-3 but has an additional 17 unique amino acid residues C-terminally. We have now developed specific anti-MASP-1 antibodies and present here a microtitre well-based inhibition assay which is used for the estimation of some basic parameters as a foundation for future clinical investigations. This, in turn, allows us to explore the relative abundances of the MASPs/MAps and the soluble pattern recognition molecules (PRMs) and hence the physiological equilibrium between these.