Identification of a novel mode of complement activation on stimulated platelets mediated by properdin

Calcyclin

“…Hourcade (2006) demonstrated, using surface plasmon resonance, that properdin promoted the association of C3b with factor B and provided a focal point for the assembly of C3bBb on a surface, suggesting that properdin may be also an initiator (Hourcade 2006;Saggu et al 2012). Furthermore, human embryonic kidney cells of Escherichia coli transfected with a vector expressing a transmembrane form of properdin on the cell surface activated the AP, suggesting that properdin can initiate complement activation (Vuagnat et al 2000;Spitzer et al 2007).…”

“…In addition, it has been demonstrated that C3(H 2 O), C3 fragments, clusterin, and immunoglobulins co-immunoprecipitate with properdin in human serum, and also, C3b 2 -natural IgG complexes stimulate complement amplification in a properdin-dependent manner (Jelezarova et al 2000). It has also been suggested that surface-bound properdin may lead to complement activation by recruiting C3b molecules derived from any of the three complement pathways or by recruiting soluble C3(H 2 O) to form a membrane-bound C3(H 2 O)Bb convertase (Saggu et al 2012). Thus, properdin has the dual ability to initiate and regulate the AP activation (Fig.…”

Local release of properdin in the cellular microenvironment: role in pattern recognition and amplification of the alternative pathway of complement

“…(Agarwal et al, 2010). However, native properdin forms do bind to necrotic cells, yeast cell wall components (Ferreira et al, 2010a), Chlamydia pneumoniae (Cortes et al, 2011), and activated platelets (Saggu et al, 2012), suggesting it is a highly selective recognition molecule. In addition, neutrophil-derived native/physiological properdin can bind to apoptotic T cells (Kemper et al, 2008) and neutrophils (Wirthmueller et al, 1997; Camous et al, 2011), while properdin, in the context of C3-deficient serum can bind to dying cells (Xu et al, 2008).…”

“…For instance, it is possible that properdin binds C3b generated during the activation of any of the three complement pathways or recruits soluble C3(H 2 O) (a C3b-like molecule) to form a membrane-bound C3(H 2 O),Bb convertase. We have recently determined that physiological forms of properdin bound to activated platelets, but not resting platelets, recruits both C3(H 2 O) and factor B, generating a functional C3(H 2 O),Bb convertase that promotes complement activation on platelets (Saggu et al, 2012), whereas platelet-bound C3(H 2 O) alone has been shown to not produce a functional convertase (Hamad et al, 2010). …”