IGM is required for efficient complement mediated phagocytosis of apoptotic cells<i>in vivo</i>

Ogden, Carol Anne; Kowalewski, Robert; Peng, You; Montenegro, Vivianne; Elkon, Keith B.

doi:10.1080/08916930500124452

Cited by 147 publications

(114 citation statements)

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“…AC can bind polyclonal IgM antibodies which then recruits C1q and activates the complement classical pathway (22)(23)(24). IgM probably binds late but not early AC (22).…”

Section: C1q Can Indirectly Opsonize Ac Through Complement Activationmentioning

confidence: 99%

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The Classical and Regulatory Functions of C1q in Immunity and Autoimmunity

et al. 2008

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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. C1q deficiency is associated with autoimmunity as well as increased susceptibility to infections. In this article, we discuss the basic properties of C1q, its expression, and classical and regulatory functions. Cellular & Molecular Immunology. 2008;5(1):9-21.

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“…AC can bind polyclonal IgM antibodies which then recruits C1q and activates the complement classical pathway (22)(23)(24). IgM probably binds late but not early AC (22).…”

Section: C1q Can Indirectly Opsonize Ac Through Complement Activationmentioning

confidence: 99%

“…C1q can directly bind AC and mediate AC phagocytosis through CD91 or LRP-1 on macrophages (18). It can also bind indirectly, through CRP and IgM, to cause complement activation and C3 deposition (24,27,73). SAP binds to chromatins in AC blebs and C1q binds to SAP to activate complement (91).…”

Section: C1q Regulates Multiple Macrophage Activitiesmentioning

confidence: 99%

The Classical and Regulatory Functions of C1q in Immunity and Autoimmunity

et al. 2008

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“…AC clearance is believed to be primarily carried out by macrophages through a specialized process, termed "efferocytosis," which is enhanced by the addition of natural IgMs (10,11) including those with anti-PC specificity (9,12). Immature dendritic cells (DCs) also have the capacity for efferocytosis and can reinforce immunologic tolerance by presenting self-antigens acquired through this process (13).…”

mentioning

confidence: 99%

MAPK phosphatase-1 is required for regulatory natural autoantibody-mediated inhibition of TLR responses

Grönwall

Chen

Vas

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Naturally arising IgM antibodies, which recognize neo-determinants on apoptotic cell (AC) membranes, are present from birth and can be further induced by AC challenge. Such naturally arising IgM antibodies can suppress proinflammatory responses to purified agonists for Toll-like receptors (TLRs), as well as block the induction of IgG immune complex-induced in vitro and in vivo pathogenic responses. To investigate the responsible mechanisms, we studied the regulatory effects of IgM anti-AC antibody on responses in bone marrow-derived dendritic cells mediated by a range of different TLRs and found that addition of IgM anti-AC inhibited the activation of the primary MAPKs: ERK1/2, JNK, and particularly p38. This was dependent on the recruitment of either C1q or mannose-binding lectin, which are both early complement factors that tag ACs for innate immune recognition. Strikingly, MAPK inhibition of responses to TLR agonists, and to lupus IgG autoantibody-chromatin immune complexes, was found to correlate with, and had an absolute requirement for, the induction and nuclear localization of MAPK phosphatase-1, a factor known to mediate glucocorticoid suppression of immune responses. Further experiments showed that natural IgM antibodies in serum exhibited the same inhibitory properties. These studies elucidate a novel homeostatic pathway by which natural antibodies, which are products of the adaptive immune system, can directly blunt inflammatory responses by recruitment and coordination of a primitive regulatory pathway of the innate immune system. apoptotic cell | autoimmunity | Dusp-1 | inflammation | MBL

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“…It binds to membrane blebs on apoptotic cells and, on the molecular level, C1q can bind to surface-exposed calreticulin, which is otherwise a resident protein of the endoplasmic reticulum in live cells (12,13). Apoptotic cells absorb polyclonal IgM, which then recruits C1q (14). Apoptotic cells are sources of self-antigens, and their impaired clearance by phagocytes, which can occur in C1q deficiency, can elicit autoantibody production (15).…”

mentioning

confidence: 99%

“…In addition, C1q also recognizes apoptotic cells and thus augments phagocytosis (12)(13)(14). It binds to membrane blebs on apoptotic cells and, on the molecular level, C1q can bind to surface-exposed calreticulin, which is otherwise a resident protein of the endoplasmic reticulum in live cells (12,13).…”

mentioning

confidence: 99%