CD93 and related family members: their role in innate immunity.

CD93 belongs to a newly described family of transmembrane glycoproteins which also includes endosialin and thrombomodulin. These cell surface proteins are grouped into a family based on similar ectodomain architecture consisting of a C-type lectin-like domain, a series of EGF-like repeats and a highly glycosylated mucin-like domain. However, recent studies suggest overlapping functions in the regulation of processes involving innate immunity and inflammation. CD93 regulates phagocytosis of apoptotic cells in vivo, a function critical to development, tissue repair and maintenance of tissue homeostasis. In addition, in vitro studies have demonstrated a role for CD93 in phagocytosis of antibody and complement opsonized particles and also in leukocyte and endothelial cell adhesion. Analysis of CD93 expression on endothelial cells in the developing mouse embryo correlates with the remodeling of blood vessels suggesting a role for CD93 in regulating angiogenesis, a process tightly linked to acute and chronic inflammation and also required for tumor metastasis. Endosialin has been characterized as a tumor specific antigen and functions in angiogenesis. Thrombomodulin is best characterized as a natural anticoagulant; however, more recent reports have illuminated the importance of thrombomodulin in the regulation of inflammation. This review discusses similarities and differences in the family members, and focuses on known and speculated functions in regulation of innate immunity.

Role of complement in Mycobacterium avium pathogenesis: in vivo and in vitro analyses of the host response to infection in the absence of complement component C3.

We investigated the importance of the host complement system in the pathogenesis of disease mediated by the intramacrophage pathogen Mycobacterium avium. Mycobacteria opsonized with complement are efficiently ingested by macrophages through various complement receptors. Furthermore, unlike other bacteria, mycobacteria can activate both the alternative and classical complement pathways in the absence of specific antibodies. Therefore, to examine the role of complement in the mycobacterial infection process in vivo, mice deficient in complement component C3 were infected with M. avium. Surprisingly, C3-deficient mice infected intravenously with M. avium displayed no difference in bacterial burden or granulomatous response compared to wild-type control mice. C3-sufficient mice and C3-deficient mice were equally susceptible to infection by M. avium regardless of the genotype at the bcg locus, a locus known to confer susceptibility to infection with intracellular pathogens. In vitro studies using mouse bone marrow-derived macrophages resulted in significant M. avium invasion of macrophages in the absence of C3; however, the kinetics of infection were delayed compared to complement-mediated invasion. The data indicate that complement does not play an essential role in mediating M. avium infections in the mouse and suggest either that other invasion mechanisms can compensate for the absence of complement-mediated entry or that complement is not a major mycobacterial opsonin in vivo.