Phagocytic cell molecules that bind the collagen-like region of C1q. Involvement in the C1q-mediated enhancement of phagocytosis.

1,037

931

Removal of apoptotic cells is essential for maintenance of tissue homeostasis, organogenesis, remodeling, development, and maintenance of the immune system, protection against neoplasia, and resolution of inflammation. The mechanisms of this removal involve recognition of the apoptotic cell surface and initiation of phagocytic uptake into a variety of cell types. Here we provide evidence that C1q and mannose binding lectin (MBL), a member of the collectin family of proteins, bind to apoptotic cells and stimulate ingestion of these by ligation on the phagocyte surface of the multifunctional protein, calreticulin (also known as the cC1qR), which in turn is bound to the endocytic receptor protein CD91, also known as the α-2-macroglobulin receptor. Use of these proteins provides another example of apoptotic cell clearance mediated by pattern recognition molecules of the innate immune system. Ingestion of the apoptotic cells through calreticulin/CD91 stimulation is further shown to involve the process of macropinocytosis, implicated as a primitive and relatively nonselective uptake mechanism for C1q- and MBL-enhanced engulfment of whole, intact apoptotic cells, as well as cell debris and foreign organisms to which these molecules may bind.

Section: Discussionmentioning

confidence: 65%

C1q and Mannose Binding Lectin Engagement of Cell Surface Calreticulin and Cd91 Initiates Macropinocytosis and Uptake of Apoptotic Cells

Ogden

deCathelineau

Hoffmann

et al. 2001

1,037

931

“…The lack of a role for C4 and C3 in the phagocytosis of apoptotic cells by resident peritoneal macrophages could be related to the activation state of the macrophages, as it is well recognized that murine resident peritoneal macrophages are unable to phagocytose C3-coated particles without additional stimuli, such as thioglycollate elicitation (24)(25)(26)(27)(28)(29). However, these resident macrophages may be able to utilize C1q as an opsonin, presumably via direct interaction with one of the candidate C1q receptors (30)(31)(32)(33). In the guinea pig, C1q is bound and degraded by both resident and thioglycollate-elicited peritoneal macrophages (34).…”

Section: Discussionmentioning

confidence: 99%

A Hierarchical Role for Classical Pathway Complement Proteins in the Clearance of Apoptotic Cells in Vivo

Taylor

Carugati

Fadok

et al. 2000

688

504

The strongest susceptibility genes for the development of systemic lupus erythematosus (SLE) in humans are null mutants of classical pathway complement proteins. There is a hierarchy of disease susceptibility and severity according to the position of the missing protein in the activation pathway, with the severest disease associated with C1q deficiency. Here we demonstrate, using novel in vivo models of apoptotic cell clearance during sterile peritonitis, a similar hierarchical role for classical pathway complement proteins in vivo in the clearance of apoptotic cells by macrophages. Our results constitute the first demonstration of an impairment in the phagocytosis of apoptotic cells by macrophages in vivo in a mammalian system. Apoptotic cells are thought to be a major source of the autoantigens of SLE, and impairment of their removal by complement may explain the link between hereditary complement deficiency and the development of SLE.

“…This molecule, a surface glycoprotein called C1qRp, binds SP-A (43), and the binding of SP-A to C1qRp enhances the M capacity for phagocytosis of opsonized targets (44). Since it was also shown that CD43 and C1qRp copurify and coimmune precipitate (45), Galgp/ CD43 and C1qRp may be components of a multimeric M complex that enhances mycobacteria binding and uptake.…”

Section: Discussionmentioning

confidence: 99%

A Macrophage Invasion Mechanism for Mycobacteria Implicating the Extracellular Domain of Cd43

Fratazzi

Manjunath

Arbeit

et al. 2000

We studied the role of CD43 (leukosialin/sialophorin), the negatively charged sialoglycoprotein of leukocytes, in the binding of mycobacteria to host cells. CD43-transfected HeLa cells bound Mycobacterium avium, but not Salmonella typhimurium or Shigella flexneri. Quantitative bacteriology showed that macrophages (Mφ) from wild-type mice (CD43+/+) bound M. avium, Mycobacterium bovis (bacillus Calmette-Guérin), and Mycobacterium tuberculosis (strain H37Rv), whereas Mφ from CD43 knockout mice (CD43−/−) did not. Fluorescence microscopy demonstrated that the associated M. avium had been ingested by the CD43+/+ Mφ. The inability of CD43−/− Mφ to bind M. avium could be restored by addition of galactoglycoprotein (Galgp), the extracellular mucin portion of CD43. The effect of Galgp is not due to opsonization of the bacteria, but required its interaction with the Mφ; other mucins had no effect. CD43 expression by the Mφ was also required for optimal induction by M. avium of tumor necrosis factor (TNF)-α production, which likewise could be reconstituted by Galgp. In contrast, interleukin (IL)-10 production by M. avium–infected Mφ was CD43 independent, demonstrating discordant regulation of TNF-α and IL-10. These findings describe a novel role of CD43 in promoting stable interaction of mycobacteria with receptors on the Mφ enabling the cells to respond specifically with TNF-α production.