Complement C1q production by osteoclasts and its regulation of osteoclast development.

C1q deficiency is the strongest known risk factor for SLE (systemic lupus erythematosus) but its endogenous cellular origin remains limitedly understood. In the present study we investigate the production of C1q by both cultured and endogenous bone osteoclasts. Blood monocytes were cultured with RANKL (receptor activator of nuclear factor κB ligand) and M-CSF (macrophage colony-stimulating factor) to generate osteoclasts and these cells expressed C1Q mRNA and also secreted C1q protein.

Molecular mechanisms for synchronized transcription of three complement C1q subunit genes in dendritic cells and macrophages.

Hereditary homozygous C1q deficiency is rare, but it almost certainly causes systemic lupus erythematosus. On the other hand, C1q levels can decline in systemic lupus erythematosus patients without apparent C1q gene defects and the versatility in C1q production is a likely cause. As an 18-subunit protein, C1q is assembled in a 1:1:1 ratio from three different subunits.

C1q regulation of dendritic cell development from monocytes with distinct cytokine production and T cell stimulation.

The causative association of complement C1q deficiency with systemic lupus erythematosus (SLE), which inevitably involves the breakdown of tolerance, remains poorly explained. Its non-hepatic, macrophage and dendritic cell (DC) origin may be highly relevant. In tissues, C1q is produced by DCs and macrophages which deposits around these cells and we ask whether this pericellular form of C1q regulates DC development from monocytes.

The classical and regulatory functions of C1q in immunity and autoimmunity.

A classical function of C1q is to bind immune complexes and initiate complement activation producing membrane lytic complexes, opsonins and anaphylatoxins. This classical pathway of complement activation is also elicited when C1q binds some other ligands. Besides complement activation, C1q also regulates cell differentiation, adhesion, migration, activation and survival.

The regulatory roles of C1q.

C1q binds to immune complexes to elicit complement-dependent microbial killing and enhance phagocytosis. Besides this classical role, C1q also opsonizes apoptotic cells for clearance by phagocytes. C1q deficiency increases susceptibility to microbial infections and is also associated with elevated autoimmunity as characterized by increased apoptotic bodies in tissues.

Identification of vaccine candidate antigens of an ESBL producing Klebsiella pneumoniae clinical strain by immunoproteome analysis.

Klebsiella pneumoniae is an opportunistic pathogen which causes pneumoniae, urinary tract infections and septicemia in immunocompromised patients. Hospital outbreaks of multidrug-resistant K. pneumoniae, especially those in neonatal wards, are often caused by strains producing the extended-spectrum-beta-lactamases (ESBLs).