C1q triggers neutrophil superoxide production by a unique CD18-dependent mechanism

Goodman, Elaine; Anderson, Donald C.; Tenner, Andrea J.

doi:10.1002/jlb.58.2.168

Cited by 36 publications

(26 citation statements)

References 4 publications

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“…The reason for the violent inflammatory cell reaction is probably multi-factorial and involves several humoral and cellular systems. For instance, C1q, C3-fragments and IgG act independently with leukocyte cell surface receptors, and they dramatically increase the adhesion and respiratory burst events in synergy [41,42]. Therefore we cannot determine the properties of the surface stimuli solely by concluding that frustrated phagocytosis occurs at an interface.…”

Section: Discussionmentioning

confidence: 99%

On the binding of complement to solid artificial surfaces in vitro

et al. 2002

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Since the realization of a complement activation capacity by artificial surfaces upon contact with blood, a common belief has evolved that charged nucleophilic surface groups such as amine (-NH 2 ) and hydroxyl (-OH) react with and eventually bind to the internal thioester in complement factor 3 (C3). A covalent ester or amide linkage is thereby supposed to form between C3b and the surface itself. In this report,we present complement surface binding data by null-ellipsometry for two nucleophilic surfaces (-NH 2 and -OH), for surfaces with immunoglobulin G (IgG) covalently bound, and for IgG spontaneously pre-adsorbed to hydrophobic silicon. The results reveal that the plasma proteins that were deposited during complement activation became eluted by sodium dodecyl sulfate (SDS). Hence the direct covalent binding between C3 and solid nucleophilic surfaces seems to be only of moderate importance, at least during shorter serum incubations. This strongly suggests that the prevalent covalent linkage model between solid artificial surfaces and C3b is not accurate.Instead we suggest a more pronounced role for C3 associations to other adsorbed proteins and/or electrostatic and hydrophobic protein-surface interactions.

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Section: Discussionmentioning

confidence: 99%

On the binding of complement to solid artificial surfaces in vitro

et al. 2002

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“…The first is that while C1q triggers superoxide production, it does not induce degranulation of primary or secondary granules (14). Other characteristics that are distinct from those of most (not all) previously described activators include the lack of pertussis toxin inhibition and the lack of a requirement for stable adherence to a surface for activation of the oxidase (13). We investigated the activity of the C1q-deficient macrophages against salmonellae by measuring the respiratory burst and the production of total NO.…”

Section: Discussionmentioning

confidence: 99%

Increased Susceptibility of C1q-Deficient Mice toSalmonella entericaSerovar Typhimurium Infection

Warren

Mastroeni

Dougan³

et al. 2002

Infect Immun

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The role of the complement system in host defense against Salmonella infection is poorly defined. Bacterial cell wall O-antigen polysaccharide can activate the alternative pathway in vitro. No studies, however, have elucidated the role of the classical pathway in immunity to Salmonella spp. in vivo. C1q-deficient mice (C1qa ؊/؊ ) on a 129/Sv genetic background and strain-matched controls were infected intraperitoneally and intravenously with Salmonella enterica serovar Typhimurium and monitored over a 14-day period. After inoculation by either route, the C1qa ؊/؊ mice were found to be significantly more susceptible to Salmonella infection. Hepatic and splenic bacterial counts, performed at various time points, showed increased numbers of colonies in complement-deficient mice compared to controls. Analysis of blood clearance showed no difference between the two experimental groups during the first 15 min. However, after 20 min and until 6 h postinfection, numbers of circulating bacteria were significantly higher in complement-deficient mice. In vitro experiments using either resident or thioglycolate-elicited peritoneal macrophages showed a significant increase in the number of bacteria inside C1q-deficient macrophages compared to controls irrespective of the serum used for opsonizing the bacteria. These findings could not be explained either by an increased bacterial uptake, analyzed in vitro and in vivo using green fluorescent protein-tagged salmonellae, or by a defect in the respiratory burst or in NO production. The data presented here suggest the possibility of novel pathways by which C1q may modulate the pathogenesis of infectious diseases caused by intracellular pathogens.

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“…Although C1q stimulation of superoxide production has been characterized in terms of its kinetics and some of the parameters required for activity [14,44], the receptor that binds C1q to mediate this effect, which has been designated as C1qR O2-, has not yet been identified. In contrast, another C1q receptor, C1qR P , expressed on myeloid and endothelial cells, that has been shown to mediate the enhancement of phagocytic capacity of monocytes and macrophages [9,45], has been cloned and sequenced [10].…”

Section: Discussionmentioning

confidence: 99%

Digestion of C1q collagen-like domain with MMPs-1, -2, -3, and -9 further defines the sequence involved in the stimulation of neutrophil superoxide production

Ruiz

Henschen-Edman

Nagase

et al. 1999

Journal of Leukocyte Biology

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C1q, a subunit of the first component (C1) of the classical complement pathway, binds to neutrophils via its collagen-like region (C1q-CLR) stimulating superoxide production. We previously identified a region of C1q-CLR, defined by fragments generated by trypsin and endoLys-C digestion, that was required for triggering this respiratory burst. To further localize that critical site, purified human C1q was digested with pepsin to generate C1q-CLR, and subsequently cleaved with the matrix metalloproteinases, MMP-1, MMP-2, MMP-3, and MMP-9. Digestion of C1q-CLR with any of these MMPs did not alter the circular dichroism spectra, demonstrating that the fragments generated had maintained the secondary structure observed in the native molecule. All fragments retained the ability to trigger superoxide production by neutrophils. Analysis of the amino acid sequences of the purified cleavage products (none of which are identical to the published cleavage site specificities for these enzymes) demonstrated that it is the C-chain, but not the A-chain of C1q, that is critical for stimulating this activity, and thus may be a target for future therapeutic intervention. J. Leukoc. Biol. 66: 416-422; 1999.

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C1q triggers neutrophil superoxide production by a unique CD18-dependent mechanism

Cited by 36 publications

References 4 publications

On the binding of complement to solid artificial surfaces in vitro

On the binding of complement to solid artificial surfaces in vitro

Increased Susceptibility of C1q-Deficient Mice toSalmonella entericaSerovar Typhimurium Infection

Digestion of C1q collagen-like domain with MMPs-1, -2, -3, and -9 further defines the sequence involved in the stimulation of neutrophil superoxide production

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